WikiVet English - User contributions [en]

Hyperparathyroidism

2014-06-15T17:02:24Z

ElzaTriegaardt: /* Introduction */

{{OpenPagesTop}}
Also Known As: '''''HPT — Parathyroid Hyperplasia — Parathyroid Adenoma — Fibrous Osteodystrophy — Grain Overload — Bran Disease — Big Head Disease — Millers Disease — Rubber Jaw — [[Metabolic Bone Disease]]'''''

==Introduction==
[[Image:parathyroidadeoma.jpg|thumb|right|200px|Parathyroid adenoma. Image courtesy of Biomed Archive.]]
[[Image:secondaryhyperparathyroidism.jpg|thumb|right|200px|Secondary hyperparathyroidism - "rubber jaw". Image courtesy of Biomed Archive.]]
[[Image:renalhyperparathyroidism.jpg|thumb|right|200px|Parathyroid hyperplasia in renal hyperparathyroidism. Image courtesy of Biomed Archive.]]
[[Image:Renal_osteodystrophy.jpg|thumb|right|200px|"Rubber jaw" in renal osteodystrophy. Image courtesy of Biomed Archive.]]
[[Image:parathyroidhyperplasia.jpg|thumb|right|200px|Parathyroid hyperplasia. Image courtesy of Biomed Archive.]]
Hyperparathyroidism is an '''[[Endocrine System - Anatomy & Physiology|endocrine]] disease''' caused by overactivity of the [[Parathyroid Glands - Anatomy & Physiology|parathyroid gland]] and consequent '''raised body levels of [[Calcium#Parathyroid Hormone|parathyroid hormone (PTH)]]'''. This in turn results in chronic hypercalaemia. It occurs in many veterinary species and can be primary or secondary.

<big>'''Primary hyperparathyroidism'''</big> originates within the parathyroid gland itself and can be due to '''glandular hyperplasia or [[Neoplasia - Pathology|neoplasia]]'''. It is most commonly due to a '''solitary benign [[Adenoma|adenoma]]''' of either the [[Parathyroid Glands - Anatomy & Physiology|internal or external parathyroid gland]].<ref>Merck Veterinary Manual, '''Primary Hyperparathyroidism''', accessed online 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/40407.htm</ref>

<big>'''Secondary hyperparathyroidism'''</big> is usually diffuse hyperplasia of the parathyroid glands due to relative hypocalcaemia and can be either renal or nutritional in origin:

Secondary '''renal hyperparathyroidism''' is a complication of '''chronic renal failure'''. This is due to relative '''hyperphosphataemia developing as a result of impaired glomerular filtration rate'''. '''Reduced vitamin D''' synthesis or absorbtion is also thought to contribute to low serum calcium levels and subsequent stimulation of the parathyroid gland. Renal production of [[Calcium#Calcitriol|calcitriol]] (active Vitamin D3) is also reduced, exacerbating the resulting [[hypercalcaemia]].

Secondary '''nutritional''' hyperparathyroidism is caused by excessive '''phosphorus intake''' causing a total or relative calcium deficiency by '''binding calcium in the gut and decreasing its absorption'''. This category encompasses '''bran disease in horses and also [[Metabolic Bone Disease|metabolic bone disease]] in reptiles'''.

==Signalment==
'''Primary''' hyperparathyroidism is seen '''infrequently in dogs and cats''', but is documented in German Shepherd Dogs.

'''Secondary renal''' hyperparathyroidism is seen '''frequently in dogs and occasionally in cats.'''

'''Nutritional''' secondary HPT can affect '''horses of all breeds and ages''' that are either supplemented with large amounts of grain based concentrates or bran, or those that escape and break into a grain store or similar. It is also seen '''occasionally in dogs and cats fed all meat diets and pigs fed unsupplemented cereal''' feed. It is most commonly seen in '''young growing animals.'''

'''[[Metabolic Bone Disease]] occurs in a wide range of captive reptiles, particularly young green iguanas'''. It is also seen in some small mammals, e.g. chinchillas and degus.

Any disease in ruminants is very rare and usually mild.

==Clinical Signs==
The main effect of hyperparathyroidism is '''[[Hypercalcaemia|hypercalcaemia]]''' which causes a range of clinical signs. '''Polydipsia, polyuria, anorexia, lethargy and depression''' are the most common signs but animals may also be '''constipated, weak, stiff-gaited, shivering and vomiting'''. Mild hypercalcaemia may not generate any overt clinical signs.

Sequelae of hyperparathyroidism include '''fibrous osteodystrophy and organ failure due to metastatic calcification.'''

'''Osteodystrophy is the [[Bones - Anatomy & Physiology#Cells|osteoclastic resorption]] of bone and replacement by weaker fibrous tissue'''. When this occurs in the '''long bones it causes shifting lameness''' and weakened bones that are '''prone to [[Fractures|fracture]]'''. Compression fractures may also occur spontaneously and if this occurs in the vertebrae, nerve dysfunction results.<ref>Merck Veterinary Manual, '''Metabolic Osteodystrophies: Fibrous Osteodystrophy: Primary Hyperparathyroidism''', accessed online 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/90313.htm</ref> Weakened bones may also cause '''tendon and ligament avulsions.'''

Fibrous osteodystrophy in the '''flat bones of the skull and face causes facial hyperostosis'''. This is seen in Bran disease or grain overload in horses and also in dogs with primary hyperparathyroidism. The face and head become '''grossly disfigured''' by excessive amounts of fibrous tissue laid down in an attempt to consolidate the weakened lamellar bone. In advanced cases, the '''mandible may become pliant''' and '''[[Teeth - Anatomy & Physiology|teeth]] may loosen''', hence the colloquial name, “rubber jaw”. This may interfere with mastication and cause '''pain, dysphagia and consequent weight loss.'''

'''Grain overload''' is also an important cause of '''severe [[Colic in Horses|colic in horses]]'''. The sudden '''increase in fermentation results in enodtoxaemia and acidosis which can be fatal.'''

Animals affected by secondary renal HPT may exhibit '''classical signs of renal insufficiency such as polydipsia, polyuria, weight loss, vomiting and dehydration'''.

'''[[Metabolic Bone Disease]] in reptiles is caused by inadequate UVB light''' which diminishes '''Vitamin D production''' in the skin. In small mammals it is usually a straightforward dietary deficiency. Affected animals often have '''limb deformities, pathological fractures, are lethargic, very weak and inappetant and may also show signs of concurrent [[Hypocalcaemia|hypocalcaemia]]'''. They may also exhibit '''[[Dysecdysis|dysecdysis]].''' Rodents may have loose or deformed teeth and faces.

==Diagnosis==
Electrolyte imbalances on blood biochemistry profiles are highly suggestive. '''Hypercalcaemia with a normal to low serum phosphorus and a low urine specific gravity''' are fairly consistent findings.

'''Urinary excretion of phosphorus''' and sometimes also calcium is increased. This can result in urolithiasis in some cases.

'''Serum PTH''' levels may be useful in diagnosing '''primary hyperparathyroidism''', but only in animals with normal renal function, i.e., those with normal creatinine and blood urea nitrogen. A '''high PTH assay along with high creatinine and blood urea nitrogen is indicative of possible renal secondary HPT'''.

'''Exploratory surgery''' of the cervical region may identify enlarged parathyroid glands if no other test is available or to confirm the diagnosis.

Animals with '''secondary renal hyperparathyroidism''' may demonstrate signs of bone loss radiographically. The bones of the '''jaw''' are affected first - with loss of the '''lamina dura, interdental and interradicular regions'''. Eventually bone loss generalises and widespread radiographic signs can be seen.

In cases of '''nutritional hyperparathyroidism, serum calcium is normal or low''' compared to high in other pathogeneses. '''Urinary excretion of phosphorus is markedly increased''' and serum PTH high. Radiographs will identify bony resorption and pathological fractures with fibrous tissue calluses.

'''[[Metabolic Bone Disease|MBD]]''' is usually identified by '''clinical signs and radiographic evidence''' of a poorly mineralised skeleton.

==Treatment==
Treatment for '''primary hyperparathyroidism''' usually requires '''surgical excision'''. [[Hypocalcaemia]] is a known post-operative complication and supplementation may be required in the short or long term management. If the hypercalcaemia persists, metastatic disease should be suspected and investigated.

Renal secondary HPT therapy is directed at '''control of the renal disease by way of specialised diet and rehydration along with supplementation of calcitriol and phosphorus binders'''.

'''Horses with bran disease should be confined until radiographs show normal bone density'''. Diet should be rectified if inadequate, and '''calcium: phosphorus ratio maintained at 1:1-3:1 for the first 2-3 months''' followed by a normal ration. If horses have also been feeding on plants high in oxalates (which can also bind calcium in the intestine) then these should be removed from the diet and limestone can be added to the diet to prevent or treat any associating signs.

Horses with colic as a result of '''grain engorgement''' require '''aggressive [[:Category:Fluid Therapy|fluid therapy]] and analgesia, and a nasogastric tube''' should be passed to alleviate any reflux. Measures should also be taken to try and prevent [[Laminitis - Horse|laninitis]] such as specialised shoes.

{{Learning
|flashcards = [[Hyperparathyroidism Flashcards]] [[Small Mammals Q&A 19]] [[Veterinary Dentistry Q&A 12]]
}}

==References==
<references/>
Lavoie, J-P., Hinchcliff, K. W (2008) '''Blackwell’s Five-Minute Veterinary Consult: Equine 2nd ed'''. ''Wiley-Blackwell, Oxford'', pp524-525.

Merck Vet Manual, '''Renal Secondary Hyperparathyroidism''', accessed 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/90314.htm

Merck Vet Manual, '''Nutritional Diseases''', accessed 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/182606.htm&word=nutritional%2csecondary

Verstraete, F. J. M. (1998) '''Self-Assessment Colour Review - Veterinary Dentistry''' ''Manson''

{{review}}

{{OpenPages}}

[[Category:Endocrine Diseases - Dog]] [[Category: Endocrine Diseases - Cat]] [[Category:Bones - Metabolic Pathology]] [[Category:Parathyroid Glands - Pathology]] [[Category:Colic in Horses]][[Category:Endocrine Diseases - Horse]]
[[Category:Expert Review]]

Hyperparathyroidism

2014-06-15T16:54:35Z

ElzaTriegaardt: /* Introduction */

{{OpenPagesTop}}
Also Known As: '''''HPT — Parathyroid Hyperplasia — Parathyroid Adenoma — Fibrous Osteodystrophy — Grain Overload — Bran Disease — Big Head Disease — Millers Disease — Rubber Jaw — [[Metabolic Bone Disease]]'''''

==Introduction==
[[Image:parathyroidadeoma.jpg|thumb|right|200px|Parathyroid adenoma. Image courtesy of Biomed Archive.]]
[[Image:secondaryhyperparathyroidism.jpg|thumb|right|200px|Secondary hyperparathyroidism - "rubber jaw". Image courtesy of Biomed Archive.]]
[[Image:renalhyperparathyroidism.jpg|thumb|right|200px|Parathyroid hyperplasia in renal hyperparathyroidism. Image courtesy of Biomed Archive.]]
[[Image:Renal_osteodystrophy.jpg|thumb|right|200px|"Rubber jaw" in renal osteodystrophy. Image courtesy of Biomed Archive.]]
[[Image:parathyroidhyperplasia.jpg|thumb|right|200px|Parathyroid hyperplasia. Image courtesy of Biomed Archive.]]
Hyperparathyroidism is an '''[[Endocrine System - Anatomy & Physiology|endocrine]] disease''' caused by overactivity of the [[Parathyroid Glands - Anatomy & Physiology|parathyroid gland]] and consequent '''raised body levels of [[Calcium#Parathyroid Hormone|parathyroid hormone (PTH)]]'''. It occurs in many veterinary species and can be primary or secondary.

<big>'''Primary hyperparathyroidism'''</big> originates within the parathyroid gland itself and can be due to '''glandular hyperplasia or [[Neoplasia - Pathology|neoplasia]]'''. It is most commonly due to a '''solitary benign [[Adenoma|adenoma]]''' of either the [[Parathyroid Glands - Anatomy & Physiology|internal or external parathyroid gland]].<ref>Merck Veterinary Manual, '''Primary Hyperparathyroidism''', accessed online 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/40407.htm</ref>

<big>'''Secondary hyperparathyroidism'''</big> is usually diffuse hyperplasia of the parathyroid glands and can be either renal or nutritional in origin:

Secondary '''renal hyperparathyroidism''' is a complication of '''chronic renal failure'''. This is due to relative '''hyperphosphataemia developing as a result of impaired glomerular filtration rate'''. '''Reduced vitamin D''' synthesis or absorbtion is also thought to contribute to low serum calcium levels and subsequent stimulation of the parathyroid gland. Renal production of [[Calcium#Calcitriol|calcitriol]] (active Vitamin D3) is also reduced, exacerbating the resulting [[hypercalcaemia]].

Secondary '''nutritional''' hyperparathyroidism is caused by excessive '''phosphorus intake''' causing a total or relative calcium deficiency by '''binding calcium in the gut and decreasing its absorption'''. This category encompasses '''bran disease in horses and also [[Metabolic Bone Disease|metabolic bone disease]] in reptiles'''.

==Signalment==
'''Primary''' hyperparathyroidism is seen '''infrequently in dogs and cats''', but is documented in German Shepherd Dogs.

'''Secondary renal''' hyperparathyroidism is seen '''frequently in dogs and occasionally in cats.'''

'''Nutritional''' secondary HPT can affect '''horses of all breeds and ages''' that are either supplemented with large amounts of grain based concentrates or bran, or those that escape and break into a grain store or similar. It is also seen '''occasionally in dogs and cats fed all meat diets and pigs fed unsupplemented cereal''' feed. It is most commonly seen in '''young growing animals.'''

'''[[Metabolic Bone Disease]] occurs in a wide range of captive reptiles, particularly young green iguanas'''. It is also seen in some small mammals, e.g. chinchillas and degus.

Any disease in ruminants is very rare and usually mild.

==Clinical Signs==
The main effect of hyperparathyroidism is '''[[Hypercalcaemia|hypercalcaemia]]''' which causes a range of clinical signs. '''Polydipsia, polyuria, anorexia, lethargy and depression''' are the most common signs but animals may also be '''constipated, weak, stiff-gaited, shivering and vomiting'''. Mild hypercalcaemia may not generate any overt clinical signs.

Sequelae of hyperparathyroidism include '''fibrous osteodystrophy and organ failure due to metastatic calcification.'''

'''Osteodystrophy is the [[Bones - Anatomy & Physiology#Cells|osteoclastic resorption]] of bone and replacement by weaker fibrous tissue'''. When this occurs in the '''long bones it causes shifting lameness''' and weakened bones that are '''prone to [[Fractures|fracture]]'''. Compression fractures may also occur spontaneously and if this occurs in the vertebrae, nerve dysfunction results.<ref>Merck Veterinary Manual, '''Metabolic Osteodystrophies: Fibrous Osteodystrophy: Primary Hyperparathyroidism''', accessed online 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/90313.htm</ref> Weakened bones may also cause '''tendon and ligament avulsions.'''

Fibrous osteodystrophy in the '''flat bones of the skull and face causes facial hyperostosis'''. This is seen in Bran disease or grain overload in horses and also in dogs with primary hyperparathyroidism. The face and head become '''grossly disfigured''' by excessive amounts of fibrous tissue laid down in an attempt to consolidate the weakened lamellar bone. In advanced cases, the '''mandible may become pliant''' and '''[[Teeth - Anatomy & Physiology|teeth]] may loosen''', hence the colloquial name, “rubber jaw”. This may interfere with mastication and cause '''pain, dysphagia and consequent weight loss.'''

'''Grain overload''' is also an important cause of '''severe [[Colic in Horses|colic in horses]]'''. The sudden '''increase in fermentation results in enodtoxaemia and acidosis which can be fatal.'''

Animals affected by secondary renal HPT may exhibit '''classical signs of renal insufficiency such as polydipsia, polyuria, weight loss, vomiting and dehydration'''.

'''[[Metabolic Bone Disease]] in reptiles is caused by inadequate UVB light''' which diminishes '''Vitamin D production''' in the skin. In small mammals it is usually a straightforward dietary deficiency. Affected animals often have '''limb deformities, pathological fractures, are lethargic, very weak and inappetant and may also show signs of concurrent [[Hypocalcaemia|hypocalcaemia]]'''. They may also exhibit '''[[Dysecdysis|dysecdysis]].''' Rodents may have loose or deformed teeth and faces.

==Diagnosis==
Electrolyte imbalances on blood biochemistry profiles are highly suggestive. '''Hypercalcaemia with a normal to low serum phosphorus and a low urine specific gravity''' are fairly consistent findings.

'''Urinary excretion of phosphorus''' and sometimes also calcium is increased. This can result in urolithiasis in some cases.

'''Serum PTH''' levels may be useful in diagnosing '''primary hyperparathyroidism''', but only in animals with normal renal function, i.e., those with normal creatinine and blood urea nitrogen. A '''high PTH assay along with high creatinine and blood urea nitrogen is indicative of possible renal secondary HPT'''.

'''Exploratory surgery''' of the cervical region may identify enlarged parathyroid glands if no other test is available or to confirm the diagnosis.

Animals with '''secondary renal hyperparathyroidism''' may demonstrate signs of bone loss radiographically. The bones of the '''jaw''' are affected first - with loss of the '''lamina dura, interdental and interradicular regions'''. Eventually bone loss generalises and widespread radiographic signs can be seen.

In cases of '''nutritional hyperparathyroidism, serum calcium is normal or low''' compared to high in other pathogeneses. '''Urinary excretion of phosphorus is markedly increased''' and serum PTH high. Radiographs will identify bony resorption and pathological fractures with fibrous tissue calluses.

'''[[Metabolic Bone Disease|MBD]]''' is usually identified by '''clinical signs and radiographic evidence''' of a poorly mineralised skeleton.

==Treatment==
Treatment for '''primary hyperparathyroidism''' usually requires '''surgical excision'''. [[Hypocalcaemia]] is a known post-operative complication and supplementation may be required in the short or long term management. If the hypercalcaemia persists, metastatic disease should be suspected and investigated.

Renal secondary HPT therapy is directed at '''control of the renal disease by way of specialised diet and rehydration along with supplementation of calcitriol and phosphorus binders'''.

'''Horses with bran disease should be confined until radiographs show normal bone density'''. Diet should be rectified if inadequate, and '''calcium: phosphorus ratio maintained at 1:1-3:1 for the first 2-3 months''' followed by a normal ration. If horses have also been feeding on plants high in oxalates (which can also bind calcium in the intestine) then these should be removed from the diet and limestone can be added to the diet to prevent or treat any associating signs.

Horses with colic as a result of '''grain engorgement''' require '''aggressive [[:Category:Fluid Therapy|fluid therapy]] and analgesia, and a nasogastric tube''' should be passed to alleviate any reflux. Measures should also be taken to try and prevent [[Laminitis - Horse|laninitis]] such as specialised shoes.

{{Learning
|flashcards = [[Hyperparathyroidism Flashcards]] [[Small Mammals Q&A 19]] [[Veterinary Dentistry Q&A 12]]
}}

==References==
<references/>
Lavoie, J-P., Hinchcliff, K. W (2008) '''Blackwell’s Five-Minute Veterinary Consult: Equine 2nd ed'''. ''Wiley-Blackwell, Oxford'', pp524-525.

Merck Vet Manual, '''Renal Secondary Hyperparathyroidism''', accessed 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/90314.htm

Merck Vet Manual, '''Nutritional Diseases''', accessed 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/182606.htm&word=nutritional%2csecondary

Verstraete, F. J. M. (1998) '''Self-Assessment Colour Review - Veterinary Dentistry''' ''Manson''

{{review}}

{{OpenPages}}

[[Category:Endocrine Diseases - Dog]] [[Category: Endocrine Diseases - Cat]] [[Category:Bones - Metabolic Pathology]] [[Category:Parathyroid Glands - Pathology]] [[Category:Colic in Horses]][[Category:Endocrine Diseases - Horse]]
[[Category:Expert Review]]

Hyperparathyroidism

2014-06-15T16:49:05Z

ElzaTriegaardt: /* Introduction */

{{OpenPagesTop}}
Also Known As: '''''HPT — Parathyroid Hyperplasia — Parathyroid Adenoma — Fibrous Osteodystrophy — Grain Overload — Bran Disease — Big Head Disease — Millers Disease — Rubber Jaw — [[Metabolic Bone Disease]]'''''

==Introduction==
[[Image:parathyroidadeoma.jpg|thumb|right|200px|Parathyroid adenoma. Image courtesy of Biomed Archive.]]
[[Image:secondaryhyperparathyroidism.jpg|thumb|right|200px|Secondary hyperparathyroidism - "rubber jaw". Image courtesy of Biomed Archive.]]
[[Image:renalhyperparathyroidism.jpg|thumb|right|200px|Parathyroid hyperplasia in renal hyperparathyroidism. Image courtesy of Biomed Archive.]]
[[Image:Renal_osteodystrophy.jpg|thumb|right|200px|"Rubber jaw" in renal osteodystrophy. Image courtesy of Biomed Archive.]]
[[Image:parathyroidhyperplasia.jpg|thumb|right|200px|Parathyroid hyperplasia. Image courtesy of Biomed Archive.]]
Hyperparathyroidism is an '''[[Endocrine System - Anatomy & Physiology|endocrine]] disease''' caused by overactivity of the [[Parathyroid Glands - Anatomy & Physiology|parathyroid gland]] and consequent '''raised body levels of [[Calcium#Parathyroid Hormone|parathyroid hormone (PTH)]]'''. It occurs in many veterinary species and can be primary or secondary.

<big>'''Primary hyperparathyroidism'''</big> originates within the parathyroid gland itself and can be due to '''glandular hyperplasia or [[Neoplasia - Pathology|neoplasia]]'''. It is most commonly due to a '''solitary benign [[Adenoma|adenoma]]''' of either the [[Parathyroid Glands - Anatomy & Physiology|internal or external parathyroid gland]].<ref>Merck Veterinary Manual, '''Primary Hyperparathyroidism''', accessed online 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/40407.htm</ref>

<big>'''Secondary hyperparathyroidism'''</big> can be either renal or nutritional in origin:

Secondary '''renal hyperparathyroidism''' is a complication of '''chronic renal failure'''. This is due to '''hyperphosphataemia developing as a result of impaired glomerular filtration rate'''. '''Reduced vitamin D''' synthesis is also thought to contribute to low serum calcium levels and subsequent stimulation of the parathyroid gland. Renal production of [[Calcium#Calcitriol|calcitriol]] is also reduced, exacerbating the resulting [[hypercalcaemia]].

Secondary '''nutritional''' hyperparathyroidism is caused by excessive '''phosphorus intake''' causing a total or relative calcium deficiency by '''binding calcium in the gut and decreasing its absorption'''. This category encompasses '''bran disease in horses and also [[Metabolic Bone Disease|metabolic bone disease]] in reptiles'''.

==Signalment==
'''Primary''' hyperparathyroidism is seen '''infrequently in dogs and cats''', but is documented in German Shepherd Dogs.

'''Secondary renal''' hyperparathyroidism is seen '''frequently in dogs and occasionally in cats.'''

'''Nutritional''' secondary HPT can affect '''horses of all breeds and ages''' that are either supplemented with large amounts of grain based concentrates or bran, or those that escape and break into a grain store or similar. It is also seen '''occasionally in dogs and cats fed all meat diets and pigs fed unsupplemented cereal''' feed. It is most commonly seen in '''young growing animals.'''

'''[[Metabolic Bone Disease]] occurs in a wide range of captive reptiles, particularly young green iguanas'''. It is also seen in some small mammals, e.g. chinchillas and degus.

Any disease in ruminants is very rare and usually mild.

==Clinical Signs==
The main effect of hyperparathyroidism is '''[[Hypercalcaemia|hypercalcaemia]]''' which causes a range of clinical signs. '''Polydipsia, polyuria, anorexia, lethargy and depression''' are the most common signs but animals may also be '''constipated, weak, stiff-gaited, shivering and vomiting'''. Mild hypercalcaemia may not generate any overt clinical signs.

Sequelae of hyperparathyroidism include '''fibrous osteodystrophy and organ failure due to metastatic calcification.'''

'''Osteodystrophy is the [[Bones - Anatomy & Physiology#Cells|osteoclastic resorption]] of bone and replacement by weaker fibrous tissue'''. When this occurs in the '''long bones it causes shifting lameness''' and weakened bones that are '''prone to [[Fractures|fracture]]'''. Compression fractures may also occur spontaneously and if this occurs in the vertebrae, nerve dysfunction results.<ref>Merck Veterinary Manual, '''Metabolic Osteodystrophies: Fibrous Osteodystrophy: Primary Hyperparathyroidism''', accessed online 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/90313.htm</ref> Weakened bones may also cause '''tendon and ligament avulsions.'''

Fibrous osteodystrophy in the '''flat bones of the skull and face causes facial hyperostosis'''. This is seen in Bran disease or grain overload in horses and also in dogs with primary hyperparathyroidism. The face and head become '''grossly disfigured''' by excessive amounts of fibrous tissue laid down in an attempt to consolidate the weakened lamellar bone. In advanced cases, the '''mandible may become pliant''' and '''[[Teeth - Anatomy & Physiology|teeth]] may loosen''', hence the colloquial name, “rubber jaw”. This may interfere with mastication and cause '''pain, dysphagia and consequent weight loss.'''

'''Grain overload''' is also an important cause of '''severe [[Colic in Horses|colic in horses]]'''. The sudden '''increase in fermentation results in enodtoxaemia and acidosis which can be fatal.'''

Animals affected by secondary renal HPT may exhibit '''classical signs of renal insufficiency such as polydipsia, polyuria, weight loss, vomiting and dehydration'''.

'''[[Metabolic Bone Disease]] in reptiles is caused by inadequate UVB light''' which diminishes '''Vitamin D production''' in the skin. In small mammals it is usually a straightforward dietary deficiency. Affected animals often have '''limb deformities, pathological fractures, are lethargic, very weak and inappetant and may also show signs of concurrent [[Hypocalcaemia|hypocalcaemia]]'''. They may also exhibit '''[[Dysecdysis|dysecdysis]].''' Rodents may have loose or deformed teeth and faces.

==Diagnosis==
Electrolyte imbalances on blood biochemistry profiles are highly suggestive. '''Hypercalcaemia with a normal to low serum phosphorus and a low urine specific gravity''' are fairly consistent findings.

'''Urinary excretion of phosphorus''' and sometimes also calcium is increased. This can result in urolithiasis in some cases.

'''Serum PTH''' levels may be useful in diagnosing '''primary hyperparathyroidism''', but only in animals with normal renal function, i.e., those with normal creatinine and blood urea nitrogen. A '''high PTH assay along with high creatinine and blood urea nitrogen is indicative of possible renal secondary HPT'''.

'''Exploratory surgery''' of the cervical region may identify enlarged parathyroid glands if no other test is available or to confirm the diagnosis.

Animals with '''secondary renal hyperparathyroidism''' may demonstrate signs of bone loss radiographically. The bones of the '''jaw''' are affected first - with loss of the '''lamina dura, interdental and interradicular regions'''. Eventually bone loss generalises and widespread radiographic signs can be seen.

In cases of '''nutritional hyperparathyroidism, serum calcium is normal or low''' compared to high in other pathogeneses. '''Urinary excretion of phosphorus is markedly increased''' and serum PTH high. Radiographs will identify bony resorption and pathological fractures with fibrous tissue calluses.

'''[[Metabolic Bone Disease|MBD]]''' is usually identified by '''clinical signs and radiographic evidence''' of a poorly mineralised skeleton.

==Treatment==
Treatment for '''primary hyperparathyroidism''' usually requires '''surgical excision'''. [[Hypocalcaemia]] is a known post-operative complication and supplementation may be required in the short or long term management. If the hypercalcaemia persists, metastatic disease should be suspected and investigated.

Renal secondary HPT therapy is directed at '''control of the renal disease by way of specialised diet and rehydration along with supplementation of calcitriol and phosphorus binders'''.

'''Horses with bran disease should be confined until radiographs show normal bone density'''. Diet should be rectified if inadequate, and '''calcium: phosphorus ratio maintained at 1:1-3:1 for the first 2-3 months''' followed by a normal ration. If horses have also been feeding on plants high in oxalates (which can also bind calcium in the intestine) then these should be removed from the diet and limestone can be added to the diet to prevent or treat any associating signs.

Horses with colic as a result of '''grain engorgement''' require '''aggressive [[:Category:Fluid Therapy|fluid therapy]] and analgesia, and a nasogastric tube''' should be passed to alleviate any reflux. Measures should also be taken to try and prevent [[Laminitis - Horse|laninitis]] such as specialised shoes.

{{Learning
|flashcards = [[Hyperparathyroidism Flashcards]] [[Small Mammals Q&A 19]] [[Veterinary Dentistry Q&A 12]]
}}

==References==
<references/>
Lavoie, J-P., Hinchcliff, K. W (2008) '''Blackwell’s Five-Minute Veterinary Consult: Equine 2nd ed'''. ''Wiley-Blackwell, Oxford'', pp524-525.

Merck Vet Manual, '''Renal Secondary Hyperparathyroidism''', accessed 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/90314.htm

Merck Vet Manual, '''Nutritional Diseases''', accessed 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/182606.htm&word=nutritional%2csecondary

Verstraete, F. J. M. (1998) '''Self-Assessment Colour Review - Veterinary Dentistry''' ''Manson''

{{review}}

{{OpenPages}}

[[Category:Endocrine Diseases - Dog]] [[Category: Endocrine Diseases - Cat]] [[Category:Bones - Metabolic Pathology]] [[Category:Parathyroid Glands - Pathology]] [[Category:Colic in Horses]][[Category:Endocrine Diseases - Horse]]
[[Category:Expert Review]]

Hyperparathyroidism

2014-06-15T16:48:17Z

ElzaTriegaardt: /* Introduction */

{{OpenPagesTop}}
Also Known As: '''''HPT — Parathyroid Hyperplasia — Parathyroid Adenoma — Fibrous Osteodystrophy — Grain Overload — Bran Disease — Big Head Disease — Millers Disease — Rubber Jaw — [[Metabolic Bone Disease]]'''''

==Introduction==
[[Image:parathyroidadeoma.jpg|thumb|right|200px|Parathyroid adenoma. Image courtesy of Biomed Archive.]]
[[Image:secondaryhyperparathyroidism.jpg|thumb|right|200px|Secondary hyperparathyroidism - "rubber jaw". Image courtesy of Biomed Archive.]]
[[Image:renalhyperparathyroidism.jpg|thumb|right|200px|Parathyroid hyperplasia in renal hyperparathyroidism. Image courtesy of Biomed Archive.]]
[[Image:Renal_osteodystrophy.jpg|thumb|right|200px|"Rubber jaw" in renal osteodystrophy. Image courtesy of Biomed Archive.]]
[[Image:parathyroidhyperplasia.jpg|thumb|right|200px|Parathyroid hyperplasia. Image courtesy of Biomed Archive.]]
Hyperparathyroidism is an '''[[Endocrine System - Anatomy & Physiology|endocrine]] disease''' caused by overactivity of the [[Parathyroid Glands - Anatomy & Physiology|parathyroid gland]] and consequent '''raised body levels of [[Calcium#Parathyroid Hormone|parathyroid hormone (PTH)]]'''. It occurs in many veterinary species and can be primary or secondary.

<big>'''Primary hyperparathyroidism'''</big> originates within the parathyroid gland itself and can be due to '''glandular hyperplasia or [[Neoplasia - Pathology|neoplasia]]'''. It is most commonly due to a '''solitary benign [[Adenoma|adenoma]]''' of either the [[Parathyroid Glands - Anatomy & Physiology|internal or external parathyroid gland]].<ref>Merck Veterinary Manual, '''Primary Hyperparathyroidism''', accessed online 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/40407.htm</ref>

<big>'''Secondary hyperparathyroidism'''</big> can be either renal or nutritional in origin:

Secondary '''renal hyperparathyroidism''' is a complication of '''chronic renal failure'''. This is due to '''hyperphosphataemia developing as a result of impaired glomerular filtration rate'''. '''Reduced vitamin D''' synthesis is also thought to contribute to low serum calcium levels and subsequent stimulation of the parathyroid gland. Renal production of [[Calcium#Calcitriol|calcitriol]] is also reduced, exacerbating the resulting [[hypercalcaemia]].

Secondary '''nutritional''' hyperparathyroidism is caused by excessive '''phosphorus intake''' causing a total or relative calcium deficiency by '''binding calcium in the gut and decreasing its absorption'''. This category encompasses '''bran disease in horses and also [[Metabolic Bone Disease|metabolic bone disease]] in reptiles'''.

==Signalment==
'''Primary''' hyperparathyroidism is seen '''infrequently in dogs and cats''', but is documented in German Shepherd Dogs.

'''Secondary renal''' hyperparathyroidism is seen '''frequently in dogs and occasionally in cats.'''

'''Nutritional''' secondary HPT can affect '''horses of all breeds and ages''' that are either supplemented with large amounts of grain based concentrates or bran, or those that escape and break into a grain store or similar. It is also seen '''occasionally in dogs and cats fed all meat diets and pigs fed unsupplemented cereal''' feed. It is most commonly seen in '''young growing animals.'''

'''[[Metabolic Bone Disease]] occurs in a wide range of captive reptiles, particularly young green iguanas'''. It is also seen in some small mammals, e.g. chinchillas and degus.

Any disease in ruminants is very rare and usually mild.

==Clinical Signs==
The main effect of hyperparathyroidism is '''[[Hypercalcaemia|hypercalcaemia]]''' which causes a range of clinical signs. '''Polydipsia, polyuria, anorexia, lethargy and depression''' are the most common signs but animals may also be '''constipated, weak, stiff-gaited, shivering and vomiting'''. Mild hypercalcaemia may not generate any overt clinical signs.

Sequelae of hyperparathyroidism include '''fibrous osteodystrophy and organ failure due to metastatic calcification.'''

'''Osteodystrophy is the [[Bones - Anatomy & Physiology#Cells|osteoclastic resorption]] of bone and replacement by weaker fibrous tissue'''. When this occurs in the '''long bones it causes shifting lameness''' and weakened bones that are '''prone to [[Fractures|fracture]]'''. Compression fractures may also occur spontaneously and if this occurs in the vertebrae, nerve dysfunction results.<ref>Merck Veterinary Manual, '''Metabolic Osteodystrophies: Fibrous Osteodystrophy: Primary Hyperparathyroidism''', accessed online 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/90313.htm</ref> Weakened bones may also cause '''tendon and ligament avulsions.'''

Fibrous osteodystrophy in the '''flat bones of the skull and face causes facial hyperostosis'''. This is seen in Bran disease or grain overload in horses and also in dogs with primary hyperparathyroidism. The face and head become '''grossly disfigured''' by excessive amounts of fibrous tissue laid down in an attempt to consolidate the weakened lamellar bone. In advanced cases, the '''mandible may become pliant''' and '''[[Teeth - Anatomy & Physiology|teeth]] may loosen''', hence the colloquial name, “rubber jaw”. This may interfere with mastication and cause '''pain, dysphagia and consequent weight loss.'''

'''Grain overload''' is also an important cause of '''severe [[Colic in Horses|colic in horses]]'''. The sudden '''increase in fermentation results in enodtoxaemia and acidosis which can be fatal.'''

Animals affected by secondary renal HPT may exhibit '''classical signs of renal insufficiency such as polydipsia, polyuria, weight loss, vomiting and dehydration'''.

'''[[Metabolic Bone Disease]] in reptiles is caused by inadequate UVB light''' which diminishes '''Vitamin D production''' in the skin. In small mammals it is usually a straightforward dietary deficiency. Affected animals often have '''limb deformities, pathological fractures, are lethargic, very weak and inappetant and may also show signs of concurrent [[Hypocalcaemia|hypocalcaemia]]'''. They may also exhibit '''[[Dysecdysis|dysecdysis]].''' Rodents may have loose or deformed teeth and faces.

==Diagnosis==
Electrolyte imbalances on blood biochemistry profiles are highly suggestive. '''Hypercalcaemia with a normal to low serum phosphorus and a low urine specific gravity''' are fairly consistent findings.

'''Urinary excretion of phosphorus''' and sometimes also calcium is increased. This can result in urolithiasis in some cases.

'''Serum PTH''' levels may be useful in diagnosing '''primary hyperparathyroidism''', but only in animals with normal renal function, i.e., those with normal creatinine and blood urea nitrogen. A '''high PTH assay along with high creatinine and blood urea nitrogen is indicative of possible renal secondary HPT'''.

'''Exploratory surgery''' of the cervical region may identify enlarged parathyroid glands if no other test is available or to confirm the diagnosis.

Animals with '''secondary renal hyperparathyroidism''' may demonstrate signs of bone loss radiographically. The bones of the '''jaw''' are affected first - with loss of the '''lamina dura, interdental and interradicular regions'''. Eventually bone loss generalises and widespread radiographic signs can be seen.

In cases of '''nutritional hyperparathyroidism, serum calcium is normal or low''' compared to high in other pathogeneses. '''Urinary excretion of phosphorus is markedly increased''' and serum PTH high. Radiographs will identify bony resorption and pathological fractures with fibrous tissue calluses.

'''[[Metabolic Bone Disease|MBD]]''' is usually identified by '''clinical signs and radiographic evidence''' of a poorly mineralised skeleton.

==Treatment==
Treatment for '''primary hyperparathyroidism''' usually requires '''surgical excision'''. [[Hypocalcaemia]] is a known post-operative complication and supplementation may be required in the short or long term management. If the hypercalcaemia persists, metastatic disease should be suspected and investigated.

Renal secondary HPT therapy is directed at '''control of the renal disease by way of specialised diet and rehydration along with supplementation of calcitriol and phosphorus binders'''.

'''Horses with bran disease should be confined until radiographs show normal bone density'''. Diet should be rectified if inadequate, and '''calcium: phosphorus ratio maintained at 1:1-3:1 for the first 2-3 months''' followed by a normal ration. If horses have also been feeding on plants high in oxalates (which can also bind calcium in the intestine) then these should be removed from the diet and limestone can be added to the diet to prevent or treat any associating signs.

Horses with colic as a result of '''grain engorgement''' require '''aggressive [[:Category:Fluid Therapy|fluid therapy]] and analgesia, and a nasogastric tube''' should be passed to alleviate any reflux. Measures should also be taken to try and prevent [[Laminitis - Horse|laninitis]] such as specialised shoes.

{{Learning
|flashcards = [[Hyperparathyroidism Flashcards]] [[Small Mammals Q&A 19]] [[Veterinary Dentistry Q&A 12]]
}}

==References==
<references/>
Lavoie, J-P., Hinchcliff, K. W (2008) '''Blackwell’s Five-Minute Veterinary Consult: Equine 2nd ed'''. ''Wiley-Blackwell, Oxford'', pp524-525.

Merck Vet Manual, '''Renal Secondary Hyperparathyroidism''', accessed 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/90314.htm

Merck Vet Manual, '''Nutritional Diseases''', accessed 25/07/2011 at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/182606.htm&word=nutritional%2csecondary

Verstraete, F. J. M. (1998) '''Self-Assessment Colour Review - Veterinary Dentistry''' ''Manson''

{{review}}

{{OpenPages}}

[[Category:Endocrine Diseases - Dog]] [[Category: Endocrine Diseases - Cat]] [[Category:Bones - Metabolic Pathology]] [[Category:Parathyroid Glands - Pathology]] [[Category:Colic in Horses]][[Category:Endocrine Diseases - Horse]]
[[Category:Expert Review]]

Calcium

2014-06-15T16:40:51Z

ElzaTriegaardt: /* Calcitriol (Activated Vitamin D3) */

{{OpenPagesTop}}
==Introduction==

Calcium is essential for many intracellular and extracellular functions. These include:

1. Enzymatic reactions and membrane stability

2. Second messenger signalling systems

3. Nerve conduction and neuromuscular transmission

4. The release of hormones by exocytosis

5. Muscle contraction (smooth and skeletal)

6. Blood coagulation

7. Milk Production

8. Structural integrity of bone and teeth

Calcium is distributed throughout the body, primarily extracellularly but also intracellularly. Intracellular calcium is maintained at very low levels (10,000 fold less than in serum); 99% of calcium is found in bone as Extracellular Matrix, in the form of hydroxyapatite.

Within the serum, 55% of the calcium is ionised - this is the biologically active form, and 10% of the calcium is in complexes such as citrate and phosphate. Together with the ionised form, this constitutes '''ultrafilterable calcium'''. 35% of the calcium is also bound to plasma proteins.

Extracellular calcium can be measured in two ways:

1. As '''total calcium''' - normal levels are '''2.45-2.83 mmol/l''' and are affected by serum protein levels.

2. As '''ionised calcium''' - normal levels are '''1.13-1.33 mmol/l'''. This is the biologically active form.

Careful sample handling and prompt measurement are essential for reliable results, which can also be affected by acid-base disturbances.

==Serum Calcium Abnormalities==

'''Elevated''' blood calcium levels ([[Hypercalcaemia|hypercalcaemia]]) can be attributed to increased parathyroid hormone (PTH) concentration and increased active vitamin D3. '''Reduced''' blood calcium levels ([[Hypocalcaemia|hypocalcaemia]]) can occur with decreased PTH, reduced Vitamin D activation and calcitonin inhibition of calcium mobilisation from bone.

==Calcium Homeostasis==

There are regulatory mechanisms which maintain calcium homeostasis:

'''Buffering'''

Exchangeable calcium is present in bone salts - amorphous calcium phosphate (CaHPO4) is in a state of reversible equilibrium with calcium and phosphorous in extracellular fluid. Exchangeable calcium is also present in mitochondria.

'''Hormonal regulation'''

Calcium levels in the body are regulated by hormones produced by the [[Renal Anatomy - Anatomy & Physiology|kidneys]], in the [[Parathyroid Glands - Anatomy & Physiology|parathyroid glands]] and in the C-Cells (also called parafollicular cells) of the [[Thyroid Gland - Anatomy & Physiology|thyroid gland]]:

1. '''Chief cells''', also known as '''principal cells''', of the parathyroid gland secrete '''Parathyroid Hormone''' (PTH) which '''INCREASES''' calcium levels in the blood.

2. The kidneys activate Vitamin D3 to create '''Active Vitamin D3''' also known as '''Calcitriol''' to '''INCREASE''' calcium levels in the blood.

3. '''C-Cells''' of the thyroid gland secrete '''Calcitonin''' which '''DECREASES''' calcium levels in the blood.

===Parathyroid Hormone (PTH)===

Synthesis of PTH is from a preprohormone of 115 amino acids into a [[Prohormones - Anatomy & Physiology|prohormone]] of 90 amino acids. This prohormone is then packaged into vesicles, as the 84 amino acid PTH molecule. It is secreted by the chief cells of the parathyroid gland continuously with a basal secretory rate of around 25% of the maximum possible rate. Secretion rate increases with a '''decrease in serum ionised calcium''' ([[Hypocalcaemia|hypocalcemia]]). Regulation of PTH is highly sensitive due to membrane receptors on chief cells coupled to G-proteins. Receptor stimulation decreases secretion; this is therefore a direct [[Negative Feedback - Anatomy & Physiology|negative feedback]] mechanism. The half-life of PTH in circulation is short - less than 10 minutes which also allows tight regulation of calcium levels. PTH is metabolised in the liver and kidneys.

PTH leads to increased calcium levels in the blood by actions on bone. There are two phases;

1. '''Fast Phase''' - This phase begins in minutes and progressively increases for hours. PTH acts on existing osteoblasts and osteocytes to increase calcium uptake from the ''bone fluid''. Nearby calcium phosphate crystals will then replace the calcium which has been removed.

2. '''Slow Phase''' - This phase involves the activation of osteoclasts and the creation of new osteoclasts, and takes ~48 hours to activate. There are no receptors for PTH on osteoclasts, so the signal comes from existing osteoblasts and osteocytes. This results in a progressive depletion of bone mineral.

PTH also leads to increased calcium levels in the blood by actions on the kidneys. PTH increases the calcium reabsorption at the level of the late distal tubules and collecting ducts. It also increases [[Magnesium|magnesium]] reabsorption. This occurs at the expense of [[Phosphorus|phosphorus]] in the proximal tubule. Thus Mg and Ca are reabsorbed and K is excreted in the urine.

PTH also leads to increased calcium levels in the blood by actions on the GI tract. Indirect effects occur via the activation of Vitamin D3.

===Calcitriol (Activated Vitamin D3)===

'''Calcitriol''', or '''1,25-dihydroxycholecalciferol''' is the biologically active metabolite of vitamin D. It is classified as a steroid hormone and acts to raise blood calcium levels.

There are two dietary sources of Vitamin D3

1. '''Vitamin D2''' is produced in plants (ergocalciferol).

2. '''Vitamin D3''' produced in animals (cholecalciferol) from cholesterol within membranes, and is fat soluble.

Vitamin D can also be converted from 7-dehydrocholesterol by ultraviolet radiation at wavelength 300nm in the [[Skin - Anatomy & Physiology|skin]]. This is not a major source in animals as the majority of the skin is covered by hair.

====Activated Vitamin D Synthesis====
Vitamin D2 or D3 from dietary sources or skin, is transported in the blood bound to ''Vitamin D Binding Globulin''. In the [[Liver - Anatomy & Physiology|liver]], it is converted to '''25-hydroxycholecalciferol''' - 25(OH)Vitamin D3. This is then stored in adipose tissue. Activation requires ''hydroxylation'' with the enzyme '1-a-Hydroxylase' which converts 25-hydroxycholecalciferol into '''1,25-dihydroxycholecalciferol''' = ACTIVE VITAMIN D3.

Regulation of this process occurs within the kidney, regulated by PTH concentration. An antagonistic enzyme to 1-a-hydroxylase is 24-hydroxylase, which creates an inactive form of vitamin D3. PTH increases the activity of 1-a-hydroxylase to increase the amount of active Vitamin D3. This molecule in itself is also responsive to the concentration of PTH.

====Actions====
There are four biological actions of Calcitriol (active Vitamin D3):

1. '''Increase calcium absorption from the intestine''' via active transport mechanisms. Calcitriol increases the synthesis of '''calbindin''' (Calcium binding protein) which transports calcium from the intestinal lumen to the vitamin D activated calcium ATPase pumps on the basolateral membrane of the enterocytes (via secondary active transport). This process takes approximately 48 hours.

2. '''Increase phosphorous absorption from the intestine''' - Phosphorous is found in grains, and is absorbed in the small intestine via active transport mechanisms which are responsive to calcitriol.

3. '''Decrease Calcium and Phosphorous excretion via the kidney''' - Calcitriol acts on the renal tubular epithelial cells to increase calcium and phosphorous reabsorption from the nephron. This action is WEAK compared to the action of PTH, which acts to reabsorb calcium but lose phosphorous from the nephron.

4. '''Normal bone functioning ([[Bones - Anatomy & Physiology#Composition of Bone|osteoclast and osteoblast functions]])''' - Calcitriol is needed for normal bone absorption and deposition. Without Vitamin D3, bone is not resorbed in response to PTH.

===Calcitonin===

Calcitonin acts to decrease calcium levels in the plasma. It is overall a weaker regulatory mechanism than PTH. Secreted by the parafollicular cells of the thyroid gland, calcitonin is stimulated by [[Hypercalcaemia|hypercalcemia]], and has the opposite effects of PTH on the bone:

1. Fast Phase - puts calcium into bone fluid by inhibiting osteoclasts' absorptive abilities.

2. Slow Phase - puts calcium into bone by reducing the formation of new osteoclasts.

There are also slight (insignificant) effects on the kidney and [[Alimentary System Overview - Anatomy & Physiology|gastrointestinal tract]].

==Calcium Homeostasis in the Rabbit==

The blood calcium concentration is not as closely regulated in the rabbit as in other species. Absorption of calcium from the gut is '''independent of metabolic need or vitamin D levels'''. Serum calcium increases in direct proportion to dietary calcium content. High concentrations of 3-4mmol/L are commonly found in rabbits fed calcium-rich diets, such as alfalfa-based diets.

The primary route of calcium excretion in rabbits is renal, unlike in other species where bile is the primary route of removal. Thus, the '''high urinary excretion''' of calcium may simply reflect the high blood concentrations.

High calcium levels along with other physiologic or pathologic processes may result in '''urolithiasis''', urine sludge, or metastatic calcification and chronic renal disease, especially if excessive vitamin D is provided.

Dilution or replacement of alfalfa-based diets might be advisable if problems occur.

{{Learning
|flashcards = [[Calcium_Homeostasis_Flash_Cards_- Anatomy & Physiology|calcium homeostasis]]
[[Small Mammals Q&A 06]]
|literature search = [http://www.cabdirect.org/search.html?q=title:(calcitriol)&fq=sc:%22ve%22 Calcitriol publications] [http://www.cabdirect.org/search.html?q=title:(%22Vitamin+D%22)&fq=sc:%22ve%22 Vitamin D publications] [http://www.cabdirect.org/search.html?q=title:(%22calcitonin%22)&fq=sc:%22ve%22 Calcitonin publications] [http://www.cabdirect.org/search.html?q=title:(calcium)+AND+od:(dogs)&fq=sc:%22ve%22 Calcium in dogs publications] [http://www.cabdirect.org/search.html?q=title:(calcium)+AND+od:(cats)&fq=sc:%22ve%22 Calcium in cats publications] [http://www.cabdirect.org/search.html?q=title:(calcium)+AND+od:(horses)&fq=sc:%22ve%22 Calcium in horses publications] [http://www.cabdirect.org/search.html?start=0&q=title:(calcium)+AND+od:(cattle)+&fq=sc:%22ve%22 Calcium in cattle publications] [http://www.cabdirect.org/search.html?q=title:(calcium)+AND+od:(sheep)+&fq=sc:%22ve%22 Calcium in sheep publications] [http://www.cabdirect.org/search.html?q=title:(calcium)+AND+od:(goats)+&fq=sc:%22ve%22 Calcium in goats publications] [http://www.cabdirect.org/search.html?it=any&q2=homeostasis&q1=calcium&calendarInput=yyyy-mm-dd&occuring1=title&show=all&rowId=1&rowId=2&rowId=3&options1=AND&options2=AND&options3=AND&occuring3=freetext&occuring2=title&publishedend=yyyy&la=any&publishedstart=yyyy&fq=sc:%22ve%22&y=8&x=47 Calcium Homeostasis publications] [http://www.cabdirect.org/search.html?it=any&q2=serum&q1=calcium&calendarInput=yyyy-mm-dd&occuring1=title&rowId=1&rowId=2&rowId=3&show=all&options1=AND&options2=AND&options3=AND&occuring3=freetext&occuring2=title&publishedend=yyyy&la=any&publishedstart=yyyy&fq=sc:%22ve%22&y=7&x=56 Serum Calcium publications] [http://www.cabdirect.org/search.html?it=any&q1=Parathyroid+Hormone&calendarInput=yyyy-mm-dd&occuring1=title&show=all&rowId=1&rowId=2&rowId=3&options1=AND&options2=AND&options3=AND&occuring3=freetext&occuring2=freetext&publishedend=yyyy&la=any&publishedstart=yyyy&fq=sc:%22ve%22&y=9&x=63 Parathyroid Hormone publications]
|full text = [http://www.cabi.org/cabdirect/FullTextPDF/2008/20083206581.pdf '''Disorders of calcium regulation in the dog and cat.''' Taboada, J.; The North American Veterinary Conference, Gainesville, USA, Small animal and exotics. Proceedings of the North American Veterinary Conference, Volume 22, Orlando, Florida, USA, 2008, 2008, pp 477-479]
}}

==References==

Harkness, J. (2010) '''Harkness and Wagner Biology and Medicine of Rabbits and Rodents''' ''John Wiley and Sons''

Cheeke, R. (2010) '''Comparative Animal Nutrition and Metabolism''' ''CABI''

{{OpenPages}}
[[Category:Electrolytes]]
[[Category:Endocrine System - Anatomy & Physiology]]
[[Category:A&P Done]][[Category:Minerals]]

Muscle Atrophy

2014-06-04T19:43:54Z

ElzaTriegaardt:

[[Image:Atrophic muscle fibres.jpg|right|thumb|100px|<center>Atrophic muscle fibres (Image sourced from Bristol Biomed Image Archive with permission)</center>]]

*Decreased myofibre or whole muscle diameter
*Myofibrils removed by disintegration -> sacrolemma too large -> forms folds
*Caused by:
**'''Disuse atrophy''' (e.g. fracture, failure to use limb, recumbency)
***Slower than denervation atrophy
***Reversible unless too prolonger or severe to cause loss of myofibres
**'''Pressure atrophy'''
***Any prolonged pressure on muscles resulting in muscle atrophy
****Abscesses, neoplasms, parasitic cysts
**'''Denervation atrophy'''
***Any interference or damage to its nerve supply results in muscle atrophy
****Can be rapid - over 50% of muscle mass may be lost in a few weeks e.g. roarer horses with [[Laryngeal Hemiplegia|laryngeal hemiplegia]]
***May be reversible if innervation re-established
***Histologically:
****Fibres become rounded in cross section unless compressed by normal fibres
****Increased concentration of nuclei as they take much longer to disintegrate
****Fibrous stroma of epimysium and endomysium condenses -> more prominent
****End result in muscle consisting of almost only fibrous tissue
***Sometimes replaced by fat tissue -> increased size of muscle = ''pseudohypertrophy''
***Muscle may have a mixture of atrophied and [[Muscle Hypertrophy|hypertrophied]] (due to increased work load) fibres if some motor units are not damaged
**'''Nutritional atrophy''' for nutrients during:
***Malnutrition, cachexia, senility
***Gradual onset except for some febrile diseases causing cachexia
***Postural muscles are not affected, sometimes even [[Muscle Hypertrophy|hypertrophy]]
***Histologically:
****Some nuclei disappear as myofibre volume is decreased
***Grossly:
****Smaller, darker, thinner muscles
***'''Senile atrophy'''
****Similar to nutritional atrophy.
****Lipofuscin pigmentation is common
*****Grossly:
******Yellow-brown / dark brown colour (esp in diaphragm)

[[Category:Muscles - Degenerative Pathology]]

Immune Mediated Haemolytic Anaemia

2014-03-06T05:06:50Z

ElzaTriegaardt: /* Haematology */

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Also known as: '''''IMHA — Autoimmune haemolytic anaemia (AIHA) — Pure red cell aplasia (PRCA)

==Introduction==
Immune-mediated haemolytic anaemia (IMHA) is the result of a [[Type II Hypersensitivity|type II antibody-mediated immune response]] directed against molecules expressed on the surface of erythrocytes. The clinical presentation of the disease depends on the isotype of antibody produced and the severity of the anaemia.

[[IgM]] antibodies are capable of fixing complement on the surface of red blood cells leading to the assembly of a membrane attack complex. This complex causes the direct lysis of erythrocytes and '''intravascular haemolysis'''. Since IgM antibodies have a high avidity, they are also able to co-ordinate the formation of large numbers of red blood cells into aggregates, a phenomenon known as '''auto-agglutination'''.

Some types of [[IgG]] antibody are able to directly activate the complement cascade but, in most cases, these antibodies are not able to cause intravascular haemolysis of agglutination and they are therefore described as '''incomplete''' antibodies. These antibodies act as opsonins and, through their interaction with Fc receptors expressed by cells of the hepatosplenic monocyte-phagocyte system (MPS), they promote the uptake and destruction of the red blood cells to which they are bound. These types of antibody therefore cause '''extravascular haemolysis'''.

IMHA may occur as a '''primary''' disease with no apparent cause or it may be '''secondary''' to another systemic insult. Possible secondary causes of IMHA include bacterial and parasite infections (including ''[[Babesia canis]]'' in dogs and ''[[Feline Infectious Anaemia|Mycoplasma haemofelis]]'' in cats), adverse drug reactions, neoplasia (especially myeloproliferative and lymphoproliferative disease) and live vaccines, although the association between vaccination and immune-mediated disease remains controversial.

The majority of cases of IMHA affect only the circulating red blood cells resulting in a strongly [[Regenerative and Non-Regenerative Anaemias|regenerative anaemia]] as the bone marrow stem cells respond to the disease. In a small number of cases, antibodies are produced that affect the stem cells of the [[Erythropoiesis|erythroid lineage]] in the bone marrow, resulting in a non-regenerative anaemia that still bears many of the same clinical features as IMHA. Although the two diseases have been considered separately in the past, they really represent two ends of a spectrum of immune-mediated disease directed at cells of the erythroid line.

The widespread lysis of red blood cells causes disease in the following ways:
*Blood '''oxygen carrying capacity''' is greatly reduced causing exercise intolerance, collapse and tissue hypoxia.
*The release of '''endogenous procoagulant''' molecules from lysed cells increases the risk of thromboembolism in various tissues, particularly the lungs, spleen and liver.

==Signalment==
Primary IMHA occurs with greater frequency in Cocker spaniels<ref>Weinkle TK, Center SA, Randolph JF, Warner KL, Barr SC, Erb HN. '''Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: 151 cases (1993-2002).''' ''J Am Vet Med Assoc. 2005 Jun 1;226(11):1869-80.''</ref><ref>McAlees TJ. '''Immune-mediated haemolytic anaemia in 110 dogs in Victoria, Australia.''' ''Aust Vet J. 2010 Jan;88(1-2):25-8.''</ref>, Old English sheepdogs and standard Poodles but any breed of dog may be affected. Middle-aged, entire female animals have been shown to be at increased risk of developing the disease in some studies.

==Diagnosis==
===Clinical Signs===
Affected animals often present acutely with sudden-onset collapse or severe exercise intolerance. On examination, the following signs may become evident:
*'''Pallor''' and/or '''[[Icterus|icterus]]''' of the mucous membranes as the release of bilirubin from lysed red blood cells may result in pre-hepatic jaundice in severely affected animals.
*A '''haemic heart murmur''' and a '''hyperdynamic peripheral pulse''' due to the reduction in viscosity of the blood.
*'''Hepatosplenomegaly''' may be apparent in cases of extravascular haemolysis where the activity of the MPS is greatly increased.
*'''Tachypnoea''' frequently occurs as animals attempt to compensate for reduced tissue oxygenation and blood oxygen carrying capacity.
*'''Dyspnoea''' may occur in animals which develop pulmonary thromboemboli or disseminated intravascular coagulation.

===Laboratory Tests===
On presentation, full biochemical and haematological analysis of blood samples are indicated to confirm the diagnosis and to obtain a baseline measurement to assess the efficacy of future treatment. Several tests are also available that have a higher specificity for the diagnosis of IMHA.

====Haematology====
Affected animals have a reduced [[Packed Cell Volume|packed cell volume]] (PCV) or haematocrit (HCT) and often a reduced haemoglobin concentration. IMHA causes a strongly [[Regenerative and Non-Regenerative Anaemias|regenerative anaemia]] and evidence of macrocytosis (increased MCV) should be apparent after 48-72 hours in dogs. A blood smear is extremely useful in evaluating cases of IMHA as [http://www.medvet.umontreal.ca/clinpath/banq-im/hematology/SpherocytesE.htm spherocytes]are often visible. These small, dense red blood cells are formed due to partial phagocytosis of red blood cells by the MPS. Polychromasia should also be visible on a blood smear from an animal undergoing regeneration and reticulocytosis can be confirmed using a supravital stain such as new methylene blue.

Reactive [[Platelet Abnormalities|thrombocytosis]] and leucocytosis may be present with any cause of anaemia.

====Biochemistry====
Serum bilirubin concentration will be elevated and this may be sufficiently severe to cause [[Icterus|icterus]]. The serum [[urea]] concentration may also be elevated as the kidneys receive less oxygen than normal causing a pre-renal azotaemia. A similar process of tissue hypoxia may also result in elevations in liver enzymes such as ALT and AST.

====Other Tests====
An '''in-saline agglutination''' test may be used to diagnose cases of IMHA that involve auto-agglutination. A drop of whole blood is mixed with a drop of plain saline on a glass slide and agitated for 30-60 seconds. A positive result is recorded if evident aggregates form but the slide should be evaluated under a microscope as rouleaux formation may result in a similar gross appearance.

A '''Coomb's test''' can be used to diagnose cases of IMHA that are caused by incomplete antibodies. The red blood cells from a patient are mixed with Coomb's antiserum (IgG antiobies directed against IgG) and, in cases where the patient has IMHA with antibodies attached to the surface of the erythrocytes, the antiserum will result in the formation of aggregates of cells. The titre of the test should be evaluated as weakly positive results may occur with other diseases.

In cases of pure red cell aplasia, a Coomb's test may still be positive but, experimentally, a definitive diagnosis can only be made by transfusing the serum of one animal to another and documenting the development of anaemia in the recipient.

A diagnosis of PRCA is made more easily by examining '''bone marrow aspirates''' (or core biopsy) for evidence of erythroid hypoplasia and a reduction in the erythroid: myeloid ratio of the marrow stem cells.

===Diagnostic Imaging===
Imaging may be indicated to rule out other potential causes of the signs observed but it is not necessary to make a diagnosis of IMHA. Hepatosplenomegaly will be the major findings on both radiographs and ultrasound scans.

==Treatment==
Affected animals often present acutely and may require intensive care. The ultimate aim of long-term treatment for IMHA is to control the autoimmune response.

===Stabilisation===
In animals that have lost a large percentage of their [[Packed Cell Volume|PCV]] acutely, it is likely that a [[Blood Products|blood transfusion]] will be required. Since animals with IMHA are not usually hypovolaemic, packed red blood cells are often transfused to replace erythrocytes without significantly expanding the plasma volume. In emergency situations, whole blood or synthetic haemoglobin molecules (such as Oxyglobin [tm]) may be used to support the oxygen carrying capacity of the patient. Oxygen may be provided to tachypnoeic and dyspnoeic patients by facemask, nasal catheter or flow-by.

===Immunosuppressive Therapy===
Whatever supportive measures are taken, the autoimmune response must be controlled to prevent the continuing lysis of red blood cells. The following types of drug are typically used to achieve this goal:
*'''Corticosteroids''' such as prednisolone and dexamethasone are used universally as a first-line treatment for IMHA as they are frequently effective, act rapidly and are available in a variety of preparations. Traditionally, very high doses of corticosteroids have been used to try to control the autoimmune response but dose rates beyond 2-3 mg/kg/day may be associated with significant adverse effects. More recently, there has been a move to add further immunosuppressive agents (see below) in a polypharmaceutical approach which allows the clinician to keep the corticosteroid dose rate at a reasonable level. Corticosteroids act to control both the cell- and antibody-mediated immune responses.
*'''Azathioprine''' is frequently used in the management of IMHA and it has effects on both cell- and antibody-mediated immune responses. It may take 3-4 weeks of treatment before the patient experiences the maximal effects of the drug. Azathioprine is a cytotoxic drug and gloves should be worn to administer tablets. Owners or keepers should be made aware that the active drug or its metabolites may be present in the saliva and other secretions of animals receiving the drug.
*'''Ciclosporin A''' is a fungal metabolite that inhibits a signaling molecule (ciclophilin) involved in T cell activation. Since B cells require T cell help to become activated, differentiate into plasma cells and produce antibodies, there is a rationale for the use of ciclosporin in cases of IMHA but there are currently no reports of its relative efficacy compared to the other immunosuppressive drugs.
*Other less commonly-used drugs include danazol (a steroid related to testosterone), mycophenolate mofetil and cyclophosphamide. Cyclophosphamide was used widely in the management of IMHA but two separate studies have shown that its use is associated with higher rates of mortality<ref>Grundy SA, Barton C. '''Influence of drug treatment on survival of dogs with immune-mediated hemolytic anemia: 88 cases (1989-1999).''' ''J Am Vet Med Assoc. 2001 Feb 15;218(4):543-6.''</ref><ref>Burgess K, Moore A, Rand W, Cotter SM. '''Treatment of immune-mediated hemolytic anemia in dogs with cyclophosphamide.''' ''J Vet Intern Med. 2000 Jul-Aug;14(4):456-62.''</ref><ref>Mason N, Duval D, Shofer FS, Giger U. '''Cyclophosphamide exerts no beneficial effect over prednisone alone in the initial treatment of acute immune-mediated hemolytic anemia in dogs: a randomized controlled clinical trial.''' ''J Vet Intern Med. 2003 Mar-Apr;17(2):206-12.''</ref>.
*'''Human gamma globulin''' is a variably popular product that is thought to act by occupying Fc receptors on cells of the MPS and therefore preventing phagocytosis of opsonised red blood cells. Studies investigating the effects of this drug have produced variable results, with some showing that it makes little difference to outcome<ref>Whelan MF, O'Toole TE, Chan DL, Rozanski EA, DeLaforcade AM, Crawford SL, Cotter SM. '''Use of human immunoglobulin in addition to glucocorticoids for the initial treatment of dogs with immune-mediated hemolytic anemia.''' ''J Vet Emerg Crit Care (San Antonio). 2009 Apr;19(2):158-64.''</ref> and others suggesting that it may be useful in the short-term control of cases that are refractory to other immunosuppressive regimes<ref>Kellerman DL, Bruyette DS. '''Intravenous human immunoglobulin for the treatment of immune-mediated hemolytic anemia in 13 dogs.''' ''J Vet Intern Med. 1997 Nov-Dec;11(6):327-32.''</ref>. Human gamma globulin is not widely available in veterinary practices and it is very expensive.
*Due to the risk of thrombo-embolism caused by the release of endogenous procoagulant molecules, low doses of '''heparin''' or '''aspirin''' are often administered to dogs with IMHA to try to prevent the formation of thrombi in the lungs, liver or spleen. There is some evidence to suggest that, if a dose of heparin is used which is individualised for a particular patient, there may be beneficial effects on survival<ref>Helmond SE, Polzin DJ, Armstrong PJ, Finke M, Smith SA. '''Treatment of immune-mediated hemolytic anemia with individually adjusted heparin dosing in dogs.''' ''J Vet Intern Med. 2010 May-Jun;24(3):597-605. Epub 2010 Apr 6.''</ref>. This effect is not observed if a constant dose of heparin is used for all patients<ref>Weinkle TK, Center SA, Randolph JF, Warner KL, Barr SC, Erb HN. '''Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: 151 cases (1993-2002).''' ''J Am Vet Med Assoc. 2005 Jun 1;226(11):1869-80.''</ref>.

===Adjunctive Therapy===
Animals with IMHA frequently suffer from concurrent vomiting, regurgitation and diarrhoea while hospitalised. These conditions are frequently managed with [[Gastroprotective Drugs|gastro-protectant drugs]] such as sucralfate, ranitidine and omeprazole to prevent the development of gastro-duodenal ulceration and [[Oesophagitis|oesophagitis]].

Antibiotics are frequently administered to animals which present with acute haemolytic crises but these should be used judiciously on a case-by-case basis.

==Prognosis==
Most mortality occurs in the first two weeks after presentation and, overall, 30-50% of animals would be expected to survive for at least one year after initial treatment for IMHA<ref>'''Idiopathic immune-mediated hemolytic anemia: treatment outcome and prognostic factors in 149 dogs.''' ''Piek CJ, Junius G, Dekker A, Schrauwen E, Slappendel RJ, Teske E.'' J Vet Intern Med. 2008 Mar-Apr;22(2):366-73. Epub 2008 Mar 10.</ref>.

{{Learning
|literature search = [http://www.cabdirect.org/search.html?options6=OR&calendarInput=yyyy-mm-dd&occuring1=title&rowId=1&rowId=2&rowId=3&rowId=4&rowId=5&rowId=6&show=all&options1=AND&occuring5=title&options2=OR&occuring4=title&options3=OR&occuring3=title&options4=OR&options5=OR&occuring2=title&publishedend=yyyy&fq=sc%3A%22ve%22&q6=PRCA&q5=%22Pure+red+cell+aplasia%22&it=any&q2=IMHA&q1=%22Immune+Mediated+Haemolytic+Anaemia%22&q4=AIHA&q3=%22Autoimmune+haemolytic+anaemia%22&la=any&publishedstart=yyyy&occuring6=title&y=8&x=45 Immune Mediated Haemolytic Anaemia publications]
|flashcards = [[Small Animal Emergency and Critical Care Medicine Q&A 20]]
}}

==References==
<references/>

{{review}}

{{OpenPages}}

[[Category:Antibody Mediated Autoimmune Diseases]]
[[Category:Immunological Diseases - Dog]][[Category:Lymphoreticular and Haematopoietic Diseases - Dog]][[Category:Lymphoreticular and Haematopoietic Diseases - Cat]][[Category:Immunological Diseases - Cat]]
[[Category:Expert Review - Small Animal]]

Immune Mediated Haemolytic Anaemia

2014-03-06T05:05:40Z

ElzaTriegaardt: /* Haematology */

{{OpenPagesTop}}
Also known as: '''''IMHA — Autoimmune haemolytic anaemia (AIHA) — Pure red cell aplasia (PRCA)

==Introduction==
Immune-mediated haemolytic anaemia (IMHA) is the result of a [[Type II Hypersensitivity|type II antibody-mediated immune response]] directed against molecules expressed on the surface of erythrocytes. The clinical presentation of the disease depends on the isotype of antibody produced and the severity of the anaemia.

[[IgM]] antibodies are capable of fixing complement on the surface of red blood cells leading to the assembly of a membrane attack complex. This complex causes the direct lysis of erythrocytes and '''intravascular haemolysis'''. Since IgM antibodies have a high avidity, they are also able to co-ordinate the formation of large numbers of red blood cells into aggregates, a phenomenon known as '''auto-agglutination'''.

Some types of [[IgG]] antibody are able to directly activate the complement cascade but, in most cases, these antibodies are not able to cause intravascular haemolysis of agglutination and they are therefore described as '''incomplete''' antibodies. These antibodies act as opsonins and, through their interaction with Fc receptors expressed by cells of the hepatosplenic monocyte-phagocyte system (MPS), they promote the uptake and destruction of the red blood cells to which they are bound. These types of antibody therefore cause '''extravascular haemolysis'''.

IMHA may occur as a '''primary''' disease with no apparent cause or it may be '''secondary''' to another systemic insult. Possible secondary causes of IMHA include bacterial and parasite infections (including ''[[Babesia canis]]'' in dogs and ''[[Feline Infectious Anaemia|Mycoplasma haemofelis]]'' in cats), adverse drug reactions, neoplasia (especially myeloproliferative and lymphoproliferative disease) and live vaccines, although the association between vaccination and immune-mediated disease remains controversial.

The majority of cases of IMHA affect only the circulating red blood cells resulting in a strongly [[Regenerative and Non-Regenerative Anaemias|regenerative anaemia]] as the bone marrow stem cells respond to the disease. In a small number of cases, antibodies are produced that affect the stem cells of the [[Erythropoiesis|erythroid lineage]] in the bone marrow, resulting in a non-regenerative anaemia that still bears many of the same clinical features as IMHA. Although the two diseases have been considered separately in the past, they really represent two ends of a spectrum of immune-mediated disease directed at cells of the erythroid line.

The widespread lysis of red blood cells causes disease in the following ways:
*Blood '''oxygen carrying capacity''' is greatly reduced causing exercise intolerance, collapse and tissue hypoxia.
*The release of '''endogenous procoagulant''' molecules from lysed cells increases the risk of thromboembolism in various tissues, particularly the lungs, spleen and liver.

==Signalment==
Primary IMHA occurs with greater frequency in Cocker spaniels<ref>Weinkle TK, Center SA, Randolph JF, Warner KL, Barr SC, Erb HN. '''Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: 151 cases (1993-2002).''' ''J Am Vet Med Assoc. 2005 Jun 1;226(11):1869-80.''</ref><ref>McAlees TJ. '''Immune-mediated haemolytic anaemia in 110 dogs in Victoria, Australia.''' ''Aust Vet J. 2010 Jan;88(1-2):25-8.''</ref>, Old English sheepdogs and standard Poodles but any breed of dog may be affected. Middle-aged, entire female animals have been shown to be at increased risk of developing the disease in some studies.

==Diagnosis==
===Clinical Signs===
Affected animals often present acutely with sudden-onset collapse or severe exercise intolerance. On examination, the following signs may become evident:
*'''Pallor''' and/or '''[[Icterus|icterus]]''' of the mucous membranes as the release of bilirubin from lysed red blood cells may result in pre-hepatic jaundice in severely affected animals.
*A '''haemic heart murmur''' and a '''hyperdynamic peripheral pulse''' due to the reduction in viscosity of the blood.
*'''Hepatosplenomegaly''' may be apparent in cases of extravascular haemolysis where the activity of the MPS is greatly increased.
*'''Tachypnoea''' frequently occurs as animals attempt to compensate for reduced tissue oxygenation and blood oxygen carrying capacity.
*'''Dyspnoea''' may occur in animals which develop pulmonary thromboemboli or disseminated intravascular coagulation.

===Laboratory Tests===
On presentation, full biochemical and haematological analysis of blood samples are indicated to confirm the diagnosis and to obtain a baseline measurement to assess the efficacy of future treatment. Several tests are also available that have a higher specificity for the diagnosis of IMHA.

====Haematology====
Affected animals have a reduced [[Packed Cell Volume|packed cell volume]] (PCV) or haematocrit (HCT) and often a reduced haemoglobin concentration. IMHA causes a strongly [[Regenerative and Non-Regenerative Anaemias|regenerative anaemia]] and evidence of macrocytosis (increased MCV) should be apparent after 48-72 hours in dogs. A blood smear is extremely useful in evaluating cases of IMHA as '''spherocytes''' [http://www.medvet.umontreal.ca/clinpath/banq-im/hematology/SpherocytesE.htm Spherocytes]are often visible. These small, dense red blood cells are formed due to partial phagocytosis of red blood cells by the MPS. Polychromasia should also be visible on a blood smear from an animal undergoing regeneration and reticulocytosis can be confirmed using a supravital stain such as new methylene blue.

Reactive [[Platelet Abnormalities|thrombocytosis]] and leucocytosis may be present with any cause of anaemia.

====Biochemistry====
Serum bilirubin concentration will be elevated and this may be sufficiently severe to cause [[Icterus|icterus]]. The serum [[urea]] concentration may also be elevated as the kidneys receive less oxygen than normal causing a pre-renal azotaemia. A similar process of tissue hypoxia may also result in elevations in liver enzymes such as ALT and AST.

====Other Tests====
An '''in-saline agglutination''' test may be used to diagnose cases of IMHA that involve auto-agglutination. A drop of whole blood is mixed with a drop of plain saline on a glass slide and agitated for 30-60 seconds. A positive result is recorded if evident aggregates form but the slide should be evaluated under a microscope as rouleaux formation may result in a similar gross appearance.

A '''Coomb's test''' can be used to diagnose cases of IMHA that are caused by incomplete antibodies. The red blood cells from a patient are mixed with Coomb's antiserum (IgG antiobies directed against IgG) and, in cases where the patient has IMHA with antibodies attached to the surface of the erythrocytes, the antiserum will result in the formation of aggregates of cells. The titre of the test should be evaluated as weakly positive results may occur with other diseases.

In cases of pure red cell aplasia, a Coomb's test may still be positive but, experimentally, a definitive diagnosis can only be made by transfusing the serum of one animal to another and documenting the development of anaemia in the recipient.

A diagnosis of PRCA is made more easily by examining '''bone marrow aspirates''' (or core biopsy) for evidence of erythroid hypoplasia and a reduction in the erythroid: myeloid ratio of the marrow stem cells.

===Diagnostic Imaging===
Imaging may be indicated to rule out other potential causes of the signs observed but it is not necessary to make a diagnosis of IMHA. Hepatosplenomegaly will be the major findings on both radiographs and ultrasound scans.

==Treatment==
Affected animals often present acutely and may require intensive care. The ultimate aim of long-term treatment for IMHA is to control the autoimmune response.

===Stabilisation===
In animals that have lost a large percentage of their [[Packed Cell Volume|PCV]] acutely, it is likely that a [[Blood Products|blood transfusion]] will be required. Since animals with IMHA are not usually hypovolaemic, packed red blood cells are often transfused to replace erythrocytes without significantly expanding the plasma volume. In emergency situations, whole blood or synthetic haemoglobin molecules (such as Oxyglobin [tm]) may be used to support the oxygen carrying capacity of the patient. Oxygen may be provided to tachypnoeic and dyspnoeic patients by facemask, nasal catheter or flow-by.

===Immunosuppressive Therapy===
Whatever supportive measures are taken, the autoimmune response must be controlled to prevent the continuing lysis of red blood cells. The following types of drug are typically used to achieve this goal:
*'''Corticosteroids''' such as prednisolone and dexamethasone are used universally as a first-line treatment for IMHA as they are frequently effective, act rapidly and are available in a variety of preparations. Traditionally, very high doses of corticosteroids have been used to try to control the autoimmune response but dose rates beyond 2-3 mg/kg/day may be associated with significant adverse effects. More recently, there has been a move to add further immunosuppressive agents (see below) in a polypharmaceutical approach which allows the clinician to keep the corticosteroid dose rate at a reasonable level. Corticosteroids act to control both the cell- and antibody-mediated immune responses.
*'''Azathioprine''' is frequently used in the management of IMHA and it has effects on both cell- and antibody-mediated immune responses. It may take 3-4 weeks of treatment before the patient experiences the maximal effects of the drug. Azathioprine is a cytotoxic drug and gloves should be worn to administer tablets. Owners or keepers should be made aware that the active drug or its metabolites may be present in the saliva and other secretions of animals receiving the drug.
*'''Ciclosporin A''' is a fungal metabolite that inhibits a signaling molecule (ciclophilin) involved in T cell activation. Since B cells require T cell help to become activated, differentiate into plasma cells and produce antibodies, there is a rationale for the use of ciclosporin in cases of IMHA but there are currently no reports of its relative efficacy compared to the other immunosuppressive drugs.
*Other less commonly-used drugs include danazol (a steroid related to testosterone), mycophenolate mofetil and cyclophosphamide. Cyclophosphamide was used widely in the management of IMHA but two separate studies have shown that its use is associated with higher rates of mortality<ref>Grundy SA, Barton C. '''Influence of drug treatment on survival of dogs with immune-mediated hemolytic anemia: 88 cases (1989-1999).''' ''J Am Vet Med Assoc. 2001 Feb 15;218(4):543-6.''</ref><ref>Burgess K, Moore A, Rand W, Cotter SM. '''Treatment of immune-mediated hemolytic anemia in dogs with cyclophosphamide.''' ''J Vet Intern Med. 2000 Jul-Aug;14(4):456-62.''</ref><ref>Mason N, Duval D, Shofer FS, Giger U. '''Cyclophosphamide exerts no beneficial effect over prednisone alone in the initial treatment of acute immune-mediated hemolytic anemia in dogs: a randomized controlled clinical trial.''' ''J Vet Intern Med. 2003 Mar-Apr;17(2):206-12.''</ref>.
*'''Human gamma globulin''' is a variably popular product that is thought to act by occupying Fc receptors on cells of the MPS and therefore preventing phagocytosis of opsonised red blood cells. Studies investigating the effects of this drug have produced variable results, with some showing that it makes little difference to outcome<ref>Whelan MF, O'Toole TE, Chan DL, Rozanski EA, DeLaforcade AM, Crawford SL, Cotter SM. '''Use of human immunoglobulin in addition to glucocorticoids for the initial treatment of dogs with immune-mediated hemolytic anemia.''' ''J Vet Emerg Crit Care (San Antonio). 2009 Apr;19(2):158-64.''</ref> and others suggesting that it may be useful in the short-term control of cases that are refractory to other immunosuppressive regimes<ref>Kellerman DL, Bruyette DS. '''Intravenous human immunoglobulin for the treatment of immune-mediated hemolytic anemia in 13 dogs.''' ''J Vet Intern Med. 1997 Nov-Dec;11(6):327-32.''</ref>. Human gamma globulin is not widely available in veterinary practices and it is very expensive.
*Due to the risk of thrombo-embolism caused by the release of endogenous procoagulant molecules, low doses of '''heparin''' or '''aspirin''' are often administered to dogs with IMHA to try to prevent the formation of thrombi in the lungs, liver or spleen. There is some evidence to suggest that, if a dose of heparin is used which is individualised for a particular patient, there may be beneficial effects on survival<ref>Helmond SE, Polzin DJ, Armstrong PJ, Finke M, Smith SA. '''Treatment of immune-mediated hemolytic anemia with individually adjusted heparin dosing in dogs.''' ''J Vet Intern Med. 2010 May-Jun;24(3):597-605. Epub 2010 Apr 6.''</ref>. This effect is not observed if a constant dose of heparin is used for all patients<ref>Weinkle TK, Center SA, Randolph JF, Warner KL, Barr SC, Erb HN. '''Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: 151 cases (1993-2002).''' ''J Am Vet Med Assoc. 2005 Jun 1;226(11):1869-80.''</ref>.

===Adjunctive Therapy===
Animals with IMHA frequently suffer from concurrent vomiting, regurgitation and diarrhoea while hospitalised. These conditions are frequently managed with [[Gastroprotective Drugs|gastro-protectant drugs]] such as sucralfate, ranitidine and omeprazole to prevent the development of gastro-duodenal ulceration and [[Oesophagitis|oesophagitis]].

Antibiotics are frequently administered to animals which present with acute haemolytic crises but these should be used judiciously on a case-by-case basis.

==Prognosis==
Most mortality occurs in the first two weeks after presentation and, overall, 30-50% of animals would be expected to survive for at least one year after initial treatment for IMHA<ref>'''Idiopathic immune-mediated hemolytic anemia: treatment outcome and prognostic factors in 149 dogs.''' ''Piek CJ, Junius G, Dekker A, Schrauwen E, Slappendel RJ, Teske E.'' J Vet Intern Med. 2008 Mar-Apr;22(2):366-73. Epub 2008 Mar 10.</ref>.

{{Learning
|literature search = [http://www.cabdirect.org/search.html?options6=OR&calendarInput=yyyy-mm-dd&occuring1=title&rowId=1&rowId=2&rowId=3&rowId=4&rowId=5&rowId=6&show=all&options1=AND&occuring5=title&options2=OR&occuring4=title&options3=OR&occuring3=title&options4=OR&options5=OR&occuring2=title&publishedend=yyyy&fq=sc%3A%22ve%22&q6=PRCA&q5=%22Pure+red+cell+aplasia%22&it=any&q2=IMHA&q1=%22Immune+Mediated+Haemolytic+Anaemia%22&q4=AIHA&q3=%22Autoimmune+haemolytic+anaemia%22&la=any&publishedstart=yyyy&occuring6=title&y=8&x=45 Immune Mediated Haemolytic Anaemia publications]
|flashcards = [[Small Animal Emergency and Critical Care Medicine Q&A 20]]
}}

==References==
<references/>

{{review}}

{{OpenPages}}

[[Category:Antibody Mediated Autoimmune Diseases]]
[[Category:Immunological Diseases - Dog]][[Category:Lymphoreticular and Haematopoietic Diseases - Dog]][[Category:Lymphoreticular and Haematopoietic Diseases - Cat]][[Category:Immunological Diseases - Cat]]
[[Category:Expert Review - Small Animal]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-03T13:17:44Z

ElzaTriegaardt: /* Prostaglandin F2α */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of FSH and LH (negative feedback at hypothalamic level by inhibiting GnRH) and thus also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. In most domestic species the corpus luteum persists for the entire length of gestation.
 The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy. This is due to the regression of the corpus luteum around day 180 of the 330-340 day gestation period.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates basophilic cells in the adenohypophysis, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the adenohypophysis, specifically the gonadotroph cells (basophilic cells).
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin inhibits FSH secretion. It does however not have any effect on the secretion of LH. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia.
 
 Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Estradiol stimulates prostaglandin synthesis while progesterone inhibits it. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female PGF2α cause luteolysis and can also cause the induction of tone and contractions within the uterus. It plays an important role in partuition in ruminants.
 
 
If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] to continue to secrete progesterone and thus maintain pregnancy. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] stimulates endometrial production of PGF2α and by the end of the [[Oestrous_Cycle_-_Anatomy_%26_Physiology|luteal phase]] the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.
 
 
Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism by PGF2α-dehydrogenase (in especially the lungs). These levels are below the threshold required to cause luteolysis as PGF2α production in early gestation is low.
 
 
The [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] is wrapped around the uterine vein. This creates a countercurrent mechanism by which the lipid soluable prostaglandins are able to diffuse from the uterine vein into the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]]. During the latter stages of the [[Oestrous_Cycle_-_Anatomy_%26_Physiology|luteal phase]] as PGF2α production increases luteolysis will occur as PGF2α Is able to reach its target in the ovary before being metabolized in systemic circulation.
 
 
Horses and pigs do not poses this countercurrent mechanism. In these spp. the [PGF2α-dehydrogenase] in systemic circulation is much lower in order to induce luteolysis when Prostaglandin concentration rises.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the cervix (it is a potent cervical dilator), [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix in animals with a soft-type cervix(equine and human) and aids stimulation of uterine contractions. It can thus be used to prepare the tract for parturition.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced mainly by the corpus luteum in most species and in the placenta(main contributor in the equine) and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin accumulates troughtout pregnancy and is released in lare amounts a few days before partus. Its target organs are the cervix, vagina, pubic symphesis and related structures. Relaxin is responsible for the softening and relaxation of connective tissues in the cervix, muscles and ligaments in the pelvis prior to parturition. Estradiol priming is required for this. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

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[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Neurotransmitters - Anatomy & Physiology

2013-11-03T13:09:57Z

ElzaTriegaardt: /* Biogenic Amines */

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==Introduction==
[[File:Synapse diag1.svg|thumb|right|250px|Synapse diagram - click image for image key]]
[[Image:Aspinall Slide5.JPG|thumb|right|250px|Image from [http://www.elsevierhealth.co.uk/veterinary-nursing/spe-60136/ Aspinall, The Complete Textbook of Veterinary Nursing], Elsevier Health Sciences, ''All rights reserved'']]
'''Neurotransmitters''' are chemicals that are used to relay, amplify and modulate signals between [[Neurons - Anatomy & Physiology|neurones]] and cells. They can be classified into two main groups; '''small-molecule transmitters (SMT)''' and '''neuropeptides'''.

SMTs are synthesised within nerve terminals via enzymes that are produced within the cell body. Within most nerve junctions, the terminal membrane of the nerve contains numerous specific transport proteins that facilitate the transport of the majority of the SMTs back into the nerve terminal, effectively recycling the neurotransmitter.

Neuropeptides are constructed of around 3 - 40 amino acid molecules that are synthesised within the cell body and are then transported to along the axon to the nerve terminal within vesicles running along microtubules. Neuropeptides are broken down by extracellular enzymes called '''peptidases''' once the neurotransmitter has been released. A small proportion of neuropeptides can bind to postsynaptic receptors in the nerve terminal membrane and can be taken up by endocytosis, although the degree of recycling of neuropeptides is lower than that of SMTs.

==Small-Molecule Neurotransmitters==
There are two major sub-groups of SMTs; '''amino acids''' and '''biogenic amines'''. All SMTs play an important role within the central nervous system with the exception of acetylcholine and norepinephrine which both are important within the peripheral nervous system.

===Amino Acids===
Amino acid '''glutamate''' is the most common '''excitatory''' SMT in the [[Nervous and Special Senses - Anatomy & Physiology#Central Nervous System (CNS)|central nervous system]] whilst '''gamma-aminobutyric acid (GABA)''' is the most common '''inhibitory''' SMT. Other amino acid SMTs include '''aspartate''' and '''glycine'''.
 
When '''glutamate''' is released it facilitates the opening of sodium channels within the post-synaptic membrane allowing sodium ions to enter the membrane and causing depolarisation. Therefore '''glutamate''' makes it easier for the cell to reach its depolarisation threshold and generate an action potential. Due to this, '''Glutamate''' is classified as an excitatory neurotransmitter.
 
'''Glycine''' is present in the spinal cord and is crucial for limb movement; in particular the motor function associated with limb reflexes. When both '''glycine''' and '''GABA''' are released they result in the opening of chloride ion channels within the post synaptic membrane resulting in the membrane becoming hyperpolarised. The cytosolic side of the membrane becomes more negative. Therefore both neurotransmitters make it more difficult for the cell to reach its depolarisation threshold to generate an action potential, thus classed as inhibitory.

<gallery widths="150px" perrow="3">
Image:GABA.svg|'''GABA'''
Image:Glutamic_Acid.png|'''Glutamic Acid'''
Image:Aspartic_Acid.png|'''Aspartic Acid'''
</gallery>

===Biogenic Amines===
Biogenic amines are synthesised from only several types of amino acids. Which amino acids are used in their formation depends on their classification.

Biogenic amines that are derived from the amino acid tyrosine are classified as '''catecholamines''' and include the SMTs '''norepinephrine (NE)''' (noradrenaline), '''epinephrine (E)''' (adrenaline), '''melatonin''' and '''dopamine (DA)'''. Adrenergic neurons release norepinephrine.

The biogenic amine that is derived from the amino acid '''tryptophane''' is called '''serotonin (5-HT)''' whilst the SMT derived from '''histidine''' is called '''histamine (HA)'''. Serotonergic neurons release serotonin. Whilst these SMTs are primarily of importance in the central nervous system, norepinephrine is predominantly found in the peripheral nervous system.
 
'''Epinephrine''' is produced by the adrenal glands. It is primarily involved in an overall activation of the sympathetic nervous system and is involved in the management of stress. '''Norepinephrine''' is also produced by adrenal glands and is involved in the initiation and maintainance of consciousness within the sympathetic nervous system. Both types of neurotransmitter utilise α or β receptors and are metabotropic.
:If an α1 adrenergic receptor is bound this will result in depolarisation of the cell and vasoconstriction of the skin and viscera.
:If a β1 receptor is bound this will also result in cellular depolarisation and an increase in heart rate and contractility.
:If a β2 receptor is bound this will result in hyperpolarisation of the cell which will cause dilation of the bronchioles of the lung.
 
'''Dopamine''' is involved in motivation as well as love and addiction. It is effectively a 'reward system' for the brain. Dopamine also affects the way in which the basal ganglia of the brain affect our movements and a shortage of dopamine can result in diseases such as Parkinson's. Dopamine is the primary neuroendocrine regulato r of [[Lactation - Endocrine Control - Anatomy & Physiology|'''prolactin''']] from the anterior [[Pituitary Gland - Anatomy & Physiology|pituitary gland]]. It is thus often called prolactin-inhibiting hormone in reproduction. Dopamine produced by the [[Hypothalamus - Anatomy & Physiology|hypothalamus]] is secreted via the hypothalamo-hypophysal blood vessels which supply the pituitary gland. Secretion of prolactin via lactotrope cells within the pituitary is inhibited by dopamine.
 
'''Serotonin''' is involved in emotions, mood, sexuality, consciousness, sleep and thermoregulation. Serotonin is utilised by the central nervous system and the gastro-intestinal system. Serotonin has also been linked to mechanisms controlling pulmonary and cerebral vascular vasoconstriction.
 
'''Melatonin''' is responsible for the regulation of onset of sleep and also for seasonal changes in the body such as winter weight gain and mating seasons.
 
'''Histamine''' release results in increased gastric secretions, dilation of capillaries, constriction of bronchial smooth muscle and decreased blood pressure.

<gallery widths="150px" perrow="3">
Image:Dopamine.png|'''Dopamine'''
Image:Epinephrine.svg|'''Epinephrine'''
</gallery>

===Other SMTs===
Other common SMTs include acetylcholine, ATP and nitric oxide.

'''Acetylcholine (ACh)''' is the most common '''excitatory''' neurotransmitter in the '''peripheral nervous system'''. Cholinergic neurons release ACh and for example, are found in the [[Muscles - Anatomy & Physiology#Neurogenic Contraction|neuromuscular junction]]. When ACh is released, it facilitates the opening of sodium channels within the post-synaptic membrane allowing sodium ions to enter the membrane and causing depolarisation. Therefore ACh makes it easier for the cell to reach its depolarisation threshold and generate an action potential. ACh has an effect on the post-synaptic membrane in skeletal muscle via '''nicotinic receptors''', which are ionotropic (see below). ACh also exerts an effect on smooth muscle via the parasympathetic nervous system via '''muscarinic receptors''', which are metabotropic (see below).

Ach is primarily involved in skeletal muscle movement within the sympathetic nervous system and visceral movements as part of the parasympathetic nervous system. When binding to '''muscarinic''' receptors, ACh can have a number of different effects dependant on the type of receptor.
:If an '''M2''' receptor is bound this will result in hyperpolarisation of the cell and a slowing of the rate of spontaneous contraction of the heart.
:If an '''M3''' or an '''M5''' receptor is bound this will result in depolarisation of the cell and contraction of smooth muscle within glands.
 
'''Adenosine triphosphate (ATP)''', as well as having many important '''intracellular functions''', is an important neurotransmitter and also has an '''autocrine''' and '''paracrine''' function. ATP belongs to the '''purines''' SMT group. All synaptic vesicles released by the terminal membrane of a nerve contain ATP as well as other neurotransmitters, although ATP can only function as a neurotransmitter in its own right if the post-synaptic terminal membrane contains ATP receptors. These ATP receptors are referred to as '''purinergic receptors'''. A pre-synaptic nerve terminal or terminal membrane never releases multiple types of SMT in addition to ATP, although it is common that neuropeptides are released in addition to ATP and SMTs. Other SMTs within the purine group include '''Guanosine triphosphate (GTP)''' and their derivatives.
 
Although '''nitric oxide (NO)''' is a neurotransmitter, its characteristics differ from those discussed above. NO relies on calcium ion activation of the enzyme '''nitric oxide synthase (NOS)''' which is found throughout the nervous system and is the enzyme that is responsible for catalysing NO from the amino acid '''L-arginine'''. NO has a very short half-life and is highly reactive. It is able to pass easily through lipid membranes. What makes NO differ from the SMTs above is that is can be released in all directions rather than pre-synaptically as per the classical SMTs. Therefore NO is able to act as a signalling pathway for the post-synaptic neuron to affect the pre-synpatic neuron. Nitrous oxide is involved in enlargement of the genital organs leading to erection.

<gallery widths="150px" perrow="3">
Image:Stickstoffmonoxid.png|'''Nitrous Oxide'''
Image:Acetylcholine.svg|'''Acetylcholine'''
</gallery>

==Neuropeptides==
The neuropeptide group of neurotransmitters contain a wide range of molecules of which only the major transmitters are included below. These include; '''enkephalin''', '''subtance P''', '''LHRH''', '''[[vasopressin]]''', '''cholecystokinin/CKK''', '''vasoactive intesinal peptide (VIP)''', '''endorphin''', '''neurotensin''', '''TRH''', '''angiotensin-II''', '''somatostatin''' and '''oxytocin'''. These neuropeptides have a wide range of effects throughout the nervous system. Many of these neuropeptides are released from nerve terminals but also as hormones from endocrine cells, cholecystokinin is an example.
 
'''Vasoactive intestinal peptide (VIP)''' plays a role within the intestines and acts to greatly increase the secretion of water and electrolytes. VIP also causes dilation of the smooth muscle within the peripheral smooth muscles and inhibits [[Gut Endocrine Function - Anatomy & Physiology|gastrin-stimulated]] gastric acid secretion. The overall effect of VIP is to increase gastric motility.
 
The neuropeptide '''vasopressin''' is responsible for metabolism and maintainance of the metabolic rate.
 
'''Substance P''' is involved in the transmission of pain from peripheral receptors to the central nervous system. It acts to increase the sensation, and therefore the consciousness, of pain and is released when [[Pain|nociceptors]] are activated. '''Enkaphalin''' acts to inhibit the release of substance P therefore acting to diminish the sensation of pain.
 
Endorphins and enkephalins are both examples of '''[[opioids]]''' and act within neuronal synapses to reduce the sensation of pain acting as natural pain killers. In humans, it has been shown that these neuropeptides also lead to a sense of euphoria. Both of these molecules belong to the same opioid category as morphine and heroin. They are produced by the pituitary gland and the hypothalamus and they chemically resemble opiates in their ability to produce analgesia and a sense of well-being. Endorphin has also been shown to stimulate dopaminergic neurones. In addition to this, endorphin can act to inhibit the release of '''substance P''' and therefore decrease the conscious perception of pain.
 
'''Cholecystokinin''' or '''CKK''' is secreted as a hormone and is involved in [[Gut Endocrine Function - Anatomy & Physiology|gastric enzyme secretion]]. CKK affects the secretion of pancreatic enzymes but also promotes feelings of satiety within the cortex of the brain following a meal. It is also involved in smooth muscle contraction within the small intestine.
 
'''Somatostatin''' or '''growth hormone-inhibiting hormone (GHIH)''' is a regulatory molecule within the endocrine system but also affects neurotransmission via it's interaction with G-protein coupled somatostatin receptors. It also inhibits the production of many other secondary hormones.

<gallery widths="150px" perrow="3">
Image:Alpha-endorphin.svg|'''Alpha-Endorphin'''
Image:NeuropeptideY_1RON.png|'''Neuropeptide Y'''
Image:Oxytocin.png|'''Oxytocin'''
</gallery>

==Other Types of Neurotransmitter==
In many neuronal synapses, not only do the post-synaptic membranes contain receptors for neurotransmitters, they also contain ion channels. In many cases the neurotransmitter receptors and ion channels are directly linked giving rise to '''ionotropic receptors'''. When a neurotransmitter binds its relevant receptor, this also may affect the gating of adjacent ion channels, either opening or closing the channel. Ionotrophic receptors such as this are responsible for the fastest type of synaptic transmission. An example of an ionotrophic receptor is '''zinc''' which is synaptically released via this mechanism. Zinc is associated with the release of another type of neurotransmitter, neuropeptide Y.

Other ion channel receptors, '''metabotrophic receptors''', exist where the ion channel is less well associated with the neurotransmitter receptors. These receptors are affected indirectly via '''G-proteins''' or '''intracellular secondary messengers''' altering the status of the gate once an appropriate signal has been received. Despite relying on an intermediate messenger system, metabotrophic receptors can also propagate rapid signal transfers, although not as rapid as ionotrophic receptors.

==Function==
The release of excitatory neurotransmitters from the pre-synaptic membrane causes channels in the post-synaptic membrane to open and cause an increase in sodium ion concentration within the postsynaptic cell and a decrease in potassium ion concentration. This leads to a depolarisation of the postsynaptic cell, which is [[Neurons - Anatomy & Physiology#Nerve Impulse Propagation|propagated further along the axon]] by an action potential (AP). Inhibitory neurotransmitters cause hyperpolarization of the postsynaptic cell making it unable to generate an action potential.

Post-synaptic receptors determine the reaction of the neurotransmitter meaning that the same neurotransmitter may cause an excitatory effect on some membranes whilst exerting an inhibitory effect on others e.g ACH can be either excitatory to skeletal muscle cells or inhibitory to both smooth muscle and cardiac muscle.

{{review}}

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[[Category:A&P Done]]
[[Category:Nervous System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T23:10:45Z

ElzaTriegaardt: /* Testosterone (T) */

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==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of FSH and LH (negative feedback at hypothalamic level by inhibiting GnRH) and thus also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. In most domestic species the corpus luteum persists for the entire length of gestation.
 The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy. This is due to the regression of the corpus luteum around day 180 of the 330-340 day gestation period.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates basophilic cells in the adenohypophysis, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the adenohypophysis, specifically the gonadotroph cells (basophilic cells).
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin inhibits FSH secretion. It does however not have any effect on the secretion of LH. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia.
 
 Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Estradiol stimulates prostaglandin synthesis while progesterone inhibits it. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female PGF2α cause luteolysis and can also cause the induction of tone and contractions within the uterus. It plays an important role in partuition in ruminants.
 
 
If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] to continue to secrete progesterone and thus maintain pregnancy. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] stimulates endometrial production of PGF2α and by the end of the [[Oestrous_Cycle_-_Anatomy_%26_Physiology|luteal phase]] the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.
 
 
Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism by PGF2α-dehydrogenase in especially the lungs). These levels are below the threshold required to cause luteolysis as PGF2α production in early gestation is low.
 
 
The [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] is wrapped around the uterine vein. This creates a countercurrent mechanism by which the lipid soluable prostaglandins are able to diffuse from the uterine vein into the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]]. During the latter stages of the [[Oestrous_Cycle_-_Anatomy_%26_Physiology|luteal phase]] as PGF2α production increases luteolysis will occur as PGF2α Is able to reach its target in the ovary before being metabolized in systemic circulation.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the cervix (it is a potent cervical dilator), [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix in animals with a soft-type cervix(equine and human) and aids stimulation of uterine contractions. It can thus be used to prepare the tract for parturition.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced mainly by the corpus luteum in most species and in the placenta(main contributor in the equine) and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin accumulates troughtout pregnancy and is released in lare amounts a few days before partus. Its target organs are the cervix, vagina, pubic symphesis and related structures. Relaxin is responsible for the softening and relaxation of connective tissues in the cervix, muscles and ligaments in the pelvis prior to parturition. Estradiol priming is required for this. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

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[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T19:44:24Z

ElzaTriegaardt: /* Prostaglandin (PGE2) */

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==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of FSH and LH (negative feedback at hypothalamic level by inhibiting GnRH) and thus also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. In most domestic species the corpus luteum persists for the entire length of gestation.
 The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy. This is due to the regression of the corpus luteum around day 180 of the 330-340 day gestation period.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the adenohypophysis, specifically the gonadotroph cells (basophilic cells).
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin inhibits FSH secretion. It does however not have any effect on the secretion of LH. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia.
 
 Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Estradiol stimulates prostaglandin synthesis while progesterone inhibits it. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female PGF2α cause luteolysis and can also cause the induction of tone and contractions within the uterus. It plays an important role in partuition in ruminants.
 
 
If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] to continue to secrete progesterone and thus maintain pregnancy. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] stimulates endometrial production of PGF2α and by the end of the [[Oestrous_Cycle_-_Anatomy_%26_Physiology|luteal phase]] the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.
 
 
Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism by PGF2α-dehydrogenase in especially the lungs). These levels are below the threshold required to cause luteolysis as PGF2α production in early gestation is low.
 
 
The [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] is wrapped around the uterine vein. This creates a countercurrent mechanism by which the lipid soluable prostaglandins are able to diffuse from the uterine vein into the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]]. During the latter stages of the [[Oestrous_Cycle_-_Anatomy_%26_Physiology|luteal phase]] as PGF2α production increases luteolysis will occur as PGF2α Is able to reach its target in the ovary before being metabolized in systemic circulation.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the cervix (it is a potent cervical dilator), [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix in animals with a soft-type cervix(equine and human) and aids stimulation of uterine contractions. It can thus be used to prepare the tract for parturition.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced mainly by the corpus luteum in most species and in the placenta(main contributor in the equine) and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin accumulates troughtout pregnancy and is released in lare amounts a few days before partus. Its target organs are the cervix, vagina, pubic symphesis and related structures. Relaxin is responsible for the softening and relaxation of connective tissues in the cervix, muscles and ligaments in the pelvis prior to parturition. Estradiol priming is required for this. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

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[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T19:39:42Z

ElzaTriegaardt: /* Prostaglandin F2αO */

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==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of FSH and LH (negative feedback at hypothalamic level by inhibiting GnRH) and thus also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. In most domestic species the corpus luteum persists for the entire length of gestation.
 The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy. This is due to the regression of the corpus luteum around day 180 of the 330-340 day gestation period.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the adenohypophysis, specifically the gonadotroph cells (basophilic cells).
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin inhibits FSH secretion. It does however not have any effect on the secretion of LH. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia.
 
 Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Estradiol stimulates prostaglandin synthesis while progesterone inhibits it. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female PGF2α cause luteolysis and can also cause the induction of tone and contractions within the uterus. It plays an important role in partuition in ruminants.
 
 
If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] to continue to secrete progesterone and thus maintain pregnancy. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] stimulates endometrial production of PGF2α and by the end of the [[Oestrous_Cycle_-_Anatomy_%26_Physiology|luteal phase]] the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.
 
 
Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism by PGF2α-dehydrogenase in especially the lungs). These levels are below the threshold required to cause luteolysis as PGF2α production in early gestation is low.
 
 
The [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] is wrapped around the uterine vein. This creates a countercurrent mechanism by which the lipid soluable prostaglandins are able to diffuse from the uterine vein into the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]]. During the latter stages of the [[Oestrous_Cycle_-_Anatomy_%26_Physiology|luteal phase]] as PGF2α production increases luteolysis will occur as PGF2α Is able to reach its target in the ovary before being metabolized in systemic circulation.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced mainly by the corpus luteum in most species and in the placenta(main contributor in the equine) and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin accumulates troughtout pregnancy and is released in lare amounts a few days before partus. Its target organs are the cervix, vagina, pubic symphesis and related structures. Relaxin is responsible for the softening and relaxation of connective tissues in the cervix, muscles and ligaments in the pelvis prior to parturition. Estradiol priming is required for this. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T19:36:36Z

ElzaTriegaardt: /* Prostaglandin F2αO */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of FSH and LH (negative feedback at hypothalamic level by inhibiting GnRH) and thus also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. In most domestic species the corpus luteum persists for the entire length of gestation.
 The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy. This is due to the regression of the corpus luteum around day 180 of the 330-340 day gestation period.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the adenohypophysis, specifically the gonadotroph cells (basophilic cells).
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin inhibits FSH secretion. It does however not have any effect on the secretion of LH. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia.
 
 Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2αO===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Estradiol stimulates prostaglandin synthesis while progesterone inhibits it. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female PGF2α cause luteolysis and can also cause the induction of tone and contractions within the uterus. It plays an important role in partuition in ruminants.
 
 
If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete progesterone and thus maintain pregnancy. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the [[Oestrous_Cycle_-_Anatomy_%26_Physiology|luteal phase]] the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.
 
 
Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism by PGF2α-dehydrogenase in especially the lungs). These levels are below the threshold required to cause luteolysis as PGF2α production in early gestation is low.
 
 
The ovarian artery is wrapped around the uterine vein. This creates a countercurrent mechanism by which the lipid soluable prostaglandins are able to diffuse from the uterine vein into the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]]. During the latter stages of the [[Oestrous_Cycle_-_Anatomy_%26_Physiology|luteal phase]] as PGF2α production increases luteolysis will occur as PGF2α Is able to reach its target in the ovary before being metabolized in systemic circulation.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced mainly by the corpus luteum in most species and in the placenta(main contributor in the equine) and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin accumulates troughtout pregnancy and is released in lare amounts a few days before partus. Its target organs are the cervix, vagina, pubic symphesis and related structures. Relaxin is responsible for the softening and relaxation of connective tissues in the cervix, muscles and ligaments in the pelvis prior to parturition. Estradiol priming is required for this. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T19:28:34Z

ElzaTriegaardt: /* Prostaglandin F2α */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of FSH and LH (negative feedback at hypothalamic level by inhibiting GnRH) and thus also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. In most domestic species the corpus luteum persists for the entire length of gestation.
 The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy. This is due to the regression of the corpus luteum around day 180 of the 330-340 day gestation period.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the adenohypophysis, specifically the gonadotroph cells (basophilic cells).
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin inhibits FSH secretion. It does however not have any effect on the secretion of LH. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia.
 
 Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2αO===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Estradiol stimulates prostaglandin synthesis while progesterone inhibits it. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female PGF2α cause luteolysis and can also cause the induction of tone and contractions within the uterus. It plays an important role in partuition in ruminants.
 
 
If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete progesterone and thus maintain pregnancy. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.
 
 
Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism by PGF2α-dehydrogenase in especially the lungs). These levels are below the threshold required to cause luteolysis as PGF2α production in early gestation is low.
 
 
The ovarian artery is wrapped around the uterine vein. This creates a countercurrent mechanism by which the lipid soluable prostaglandins are able to diffuse from the uterine vein into the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]]. During the latter stages of the luteal phase as PGF2α production increases luteolysis will occur as PGF2α Is able to reach its target in the ovary before being metabolized in systemic circulation.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced mainly by the corpus luteum in most species and in the placenta(main contributor in the equine) and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin accumulates troughtout pregnancy and is released in lare amounts a few days before partus. Its target organs are the cervix, vagina, pubic symphesis and related structures. Relaxin is responsible for the softening and relaxation of connective tissues in the cervix, muscles and ligaments in the pelvis prior to parturition. Estradiol priming is required for this. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

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[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T16:24:26Z

ElzaTriegaardt: /* Relaxin */

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==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of FSH and LH (negative feedback at hypothalamic level by inhibiting GnRH) and thus also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. In most domestic species the corpus luteum persists for the entire length of gestation.
 The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy. This is due to the regression of the corpus luteum around day 180 of the 330-340 day gestation period.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the adenohypophysis, specifically the gonadotroph cells (basophilic cells).
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin inhibits FSH secretion. It does however not have any effect on the secretion of LH. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia.
 
 Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced mainly by the corpus luteum in most species and in the placenta(main contributor in the equine) and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin accumulates troughtout pregnancy and is released in lare amounts a few days before partus. Its target organs are the cervix, vagina, pubic symphesis and related structures. Relaxin is responsible for the softening and relaxation of connective tissues in the cervix, muscles and ligaments in the pelvis prior to parturition. Estradiol priming is required for this. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T16:15:29Z

ElzaTriegaardt: /* Inhibin */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of FSH and LH (negative feedback at hypothalamic level by inhibiting GnRH) and thus also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. In most domestic species the corpus luteum persists for the entire length of gestation.
 The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy. This is due to the regression of the corpus luteum around day 180 of the 330-340 day gestation period.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the adenohypophysis, specifically the gonadotroph cells (basophilic cells).
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin inhibits FSH secretion. It does however not have any effect on the secretion of LH. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia.
 
 Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T16:14:40Z

ElzaTriegaardt: /* Inhibin */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of FSH and LH (negative feedback at hypothalamic level by inhibiting GnRH) and thus also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. In most domestic species the corpus luteum persists for the entire length of gestation.
 The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy. This is due to the regression of the corpus luteum around day 180 of the 330-340 day gestation period.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the adenohypophysis, specifically the gonadotroph cells (basophilic cells).
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin inhibits FSH secretion. It does however not have any effect on the secretion of LH. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia.
 
 
 Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

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[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T16:06:49Z

ElzaTriegaardt: /* Progesterone During Pregnancy */

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==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of FSH and LH (negative feedback at hypothalamic level by inhibiting GnRH) and thus also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. In most domestic species the corpus luteum persists for the entire length of gestation.
 The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy. This is due to the regression of the corpus luteum around day 180 of the 330-340 day gestation period.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T15:54:15Z

ElzaTriegaardt: /* Progesterone (P4) */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T15:53:38Z

ElzaTriegaardt: /* Estradiol (E2) */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T15:49:51Z

ElzaTriegaardt: /* Estradiol (E2) */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

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[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T15:49:22Z

ElzaTriegaardt: /* Estradiol (E2) */

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==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T15:48:52Z

ElzaTriegaardt: /* Estradiol (E2) */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T15:47:58Z

ElzaTriegaardt: /* Estradiol (E2) */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 
 
 Corpus luteum: Luteolytic (bovine and ovine) but luteotrophic (equine and porcine)
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

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[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T15:45:26Z

ElzaTriegaardt: /* Progesterone (P4) */

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==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, sensitization of the endometrium to oxytocin, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T15:44:37Z

ElzaTriegaardt: /* Estradiol (E2) */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, hyperaemia, oedema
 Cervix: relaxation, liquification of mucous plug (causing the bull string)
 Uterus: stimulates uterine gland development, sensitization of the endometrium to oxytocin, immune activation (local), leucocyte infiltration, secretion of PGF2a and PGE2
 Fallopian tube: increased motility and cilia activity
 Mammary gland: stimulates mammary duct development
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T15:38:00Z

ElzaTriegaardt: /* Progesterone (P4) */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

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[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T15:36:56Z

ElzaTriegaardt: /* Progesterone (P4) */

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==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
 Cervix: closure, formation of the mucous plug
 Uterus: stimulates uterine gland secretions, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
 Fallopian tube: increased secretion, decreased motility
 Mammary gland: stimulates lobulo-alveolar development
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T15:35:07Z

ElzaTriegaardt: /* Progesterone (P4) */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.

'''Effects on reproductive organs:'''
 Vagina: slight mucous secretion, paleness, exfoliation
Cervix: closure, formation of the mucous plug
Uterus: stimulates uterine gland secretions, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
Fallopian tube: increased secretion, decreased motility
Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T15:34:03Z

ElzaTriegaardt: /* Progesterone (P4) */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced by the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]] as well as by the feto-placental unit and in the zona reticularis of the adrenal cortex (to a lesser extent). More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilized oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.

'''Effects on reproductive organs:'''
Vagina: slight mucous secretion, paleness, exfoliation
Cervix: closure, formation of the mucous plug
Uterus: stimulates uterine gland secretions, decreases uterine motility, immunosuppression, inhibition of PGF2a and PGE2
Fallopian tube: increased secretion, decreased motility
Mammary gland: stimulates lobulo-alveolar development
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

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[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T14:55:04Z

ElzaTriegaardt: /* Estradiol (E2) */

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==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the Zona reticularis of the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]]. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced in the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]]. More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilised oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reproductive Hormones Overview - Anatomy & Physiology

2013-11-02T14:53:16Z

ElzaTriegaardt: /* Estradiol (E2) */

{{OpenPagesTop}}
==Introduction==
Reproductive hormones often have multiple roles and operate via [[Negative_Feedback_-_Anatomy_%26_Physiology|negative feedback systems]]. The information below will provide the main reproductive hormones in domestic species and their functions.
 
 
Please note that due to the complexity of the interactions of some of the hormones noted below, it has not been possible to fully explain the effects of the hormone on this page. Therefore this reproductive hormones overview should be utilised alongside more detailed information on specific physiology such as the reproduction pages which can be found within the '''WikiAnatomy & Physiology''' section on the top of the bar on the left.

==Reproductive Hormones==
===Gonadotropin Releasing Hormone (GnRH)===
GnRH is a neuropeptide (a decapeptide) that is produced in the '''hypothalamic surge''' and '''tonic''' centres. In the male and the female, the target tissue is the '''anterior pituitary gland''', specifically '''Gonadotroph cells'''. In males and females, secretion of GnRH results in the release of '''Follicle Stimulating Hormone (FSH)''' and '''Leutinising Hormone (LH)''' from the anterior pituitary gland.
 
 
GnRH-producing neurons are stimulated into production in response to spontaneous rhythms and by sensory impulses from sensory inputs derived from the external environment. Alterations in the internal conditions of the body can also result in altered GnRH production. For example in some species such as the sheep, there is seasonal sexual activity and the cerebral cortex, hypothalamus, pituitary and testes interact to regulate functions further along the signalling chain.
 
 
In females when the oestrogen concentration prior to ovulation reaches a certain threshold, large quantities of GnRH are released in the form of a surge. This results in a corresponding peak in LH that stimulates ovulation. In females this surge centre is often called the '''preovulatory centre'''. In males this surge centre becomes inactivated during fetal life due to the brain maturation effects of estradiol (see section below) being able to pass through the blood brain barrier in males, please see the [[Reproductive_System_Development#Sexual_Differentiation_of_the_Brain|reproductive development of the brain]] for more details. In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.
 
 
Although the hypothalamus via GnRH stimulates the secretion of LH and FSH, it cannot regulate LH and FSH independantly. Therefore another hormone produced from the developing ovarian follicle in the female and sertoli cells in the male acts as a negative feedback mechanism for FSH. Sex hormones also alter the level of production of GnRH from the hypothalamus via a negative feedback system. High concentrations of progesterone or testosterone will reduce the secretion of GnRH and also therefore the secretion of LH and FSH.

===Luteinising Hormone (LH)===
LH is a type of glycoprotein that is produced in the '''anterior pituitary''' via gonadotroph cells and serves to regulate the function of the gonads. In males LH stimulates the production and secretion of testosterone from the testes via '''leydig cells'''. In females LH stimulates the production of oestrogens and progesterone from the ovary via [[Follicles_-_Anatomy_%26_Physiology#Primary_Follicle|'''theca interna cells''']] and '''luteal cells'''. Concentrations of LH increase during ovulation and with the formation of the corpora lutea with progesterone secretion. The secretion of LH is regulated via the secretion of GnRH (see earlier section).
 
 
As shown previously, in males there are between 4 to 12 GnRH pulses per day and this therefore means that LH also peaks throughout the day. During these peaks, the production and secretion of testosterone increases. Testosterone secretion also is pulsatile.

===Follicle Stimulating Hormone (FSH)===
FSH is a type of glycoprotein that is produced in the '''anterior pituitary''' via '''gonadotroph cells'''. FSH secretion is regulated by GnRH from the hypothalamus. The target tissue of FSH in males are the '''sertoli cells''' within the testes and in the female the '''granulosa cells''' of the ovary. FSH stimulates the maturation of germ cells within the testes and ovaries. In the female it also stimulates follicular development and oestradiol synthesis.
 
 
In the male FSH also stimulates the secretion of '''inhibin''' which has a negative feedback directly to the anterior pituitary. Although GnRH is released in a pulsatile fashion and the other gonadotropic hormone LH is therefore also pulsatile, FSH concentrations do not fluctuate as much as that of LH. This is because of the added regulatory feedback mechanism of inhibin within the regulatory pathways for FSH secretion.

===Prolactin (PRL)===
Prolactin is a protein that is produced from by the '''anterior pituitary''' via '''lactotroph cells'''. This hormone exerts a stimulatory effect on milk synthesis within the mammary glands. It has also been shown to have some degree of gonadal function in some domestic species and rodents. In birds increased concentrations of prolactin have been linked with brooding behaviours and the associated metabolic changes that birds undergo during brooding.
 
 
Prolactin secretion is regulated by the hypothalamus which produces several neurohormones that affect prolactin concentrations. The most important within this is [[Neurotransmitters_-_Anatomy_%26_Physiology#Biogenic_Amines|'''dopamine''']] (or prolactin inhibitory hormone, PRL-IH) which exerts a totally dominant inhibitory action on prolactin synthesis. The hypothalamic regulation of prolactin secretion is via signals from the central nervous system. Prolactin synthesis is increased when the mother is suckling via a reflex stimulation of the teats. This stimulation reflex reduces the secretion of dopamine and increases the hormone '''prolactin releasing hormone''' (PRL-RH). Once prolactin binds to it's target receptors within the mammary gland cells, it activates an intracellular tyrosine kinase. When this occurs in the developing animal this binding can also cause the differentiation of mammary epithelial cells during pregnancy. The half-life of prolactin is approximately 20mins.
 
 
Estradiol can also have an effect on the prolactin producing cells within the anterior pituitary and is responsible for increased concentrations of prolactin in females undergoing puberty and may also contribute to the increased concentrations during late pregnancy.

===Oxytocin (OT)===
OT is a neuropeptide (a octapeptide) which is synthesised in the '''hypothalamus''' and stored in the posterior pituitary. OT is primarily involved in upregulating the activity of smooth muscle cells in the uterus and the smooth muscles surrounding the alveoli ducts of the mammary glands. At parturition, OT causes strong contractions from the myometrium. OT is also essential for 'milk let-down' in most domestic species.
 
 
OT binds to receptors in the membrane of target cells which activates phospholipase C. OT facilitates the generation of the driving pressure behind pushing the milk towards the large excretory ducts and the teats.

===Estradiol (E2)===
Estradiol (E2) is a steroid hormone and is part of the oestrogens group of hormones and is the principle oestrogen in females. '''Estrone''' and '''estriol''' are chemically similar to estradiol but are found in lower concentrations and have a lower estrogenic activity. Production of oestrogens occurs in the ovary via [[Follicles_-_Anatomy_%26_Physiology#General_Structure|'''granulosa cells''']], the [[Placenta_-_Anatomy_%26_Physiology|placenta]] and the [[Adrenal_Glands_-_Anatomy_%26_Physiology#Adrenal_Cortex|adrenal cortex]] in the Zona reticularis. In males in it is produced in sertoli cells found in the testes. Estradiol is synthesised from cholestrol.
 
 
Oestrogens have a number of functions related to reproduction and other areas of physiology. In relation to the reproductive role of oestrogens, they stimulate follicular growth and maturation, induce the female to begin displaying oestrous behaviour to facilitate mating, prepare the external genitalia for copulation and create favourable conditions for the development of fertilised egg cells. Oestrogens also contribute to the growth and development of mammary tissue and prepare the uterus for parturition.
 
 
Where oestrogens stimulate growth of follicles in the ovaries, oestrogens secreted from the ovary in the '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Follicular_Phase|follicular phase]]''' ('''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Pro-Oestrus|proestrous]]''' and '''[[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|oestrous]]''') lead to hypertrophy of the epithelium and the endometrium. Secretory glands within the uterus enlarge and secretion is initiated leading to thickening of tissues. The blood vessels supplying the uterus and external genitalia dilate and blood flow to these areas increases significantly. Oedema occurs within the uterus and surrounding connective tissues. Oestrogen also causes increased uterine muscle tone. In the cervix oestrogens stimulate increased mucus secretion and the vaginal epithelium becomes keratinised.
 
 
In males the target tissue is the brain where it causes maturation of the brain during development. This maturation process ensures the appropriate development of male sexual behaviours. E2 in the male also inhibits long bone growth.

===Progesterone (P4)===
Progesterone is a steroid hormone that along with oestrogens is based on a cholesterol molecule produced by the corpus luteum and the placenta using cholesterol as the base molecule. Progesterone is produced in the [[Corpus_Luteum_-_Anatomy_%26_Physiology|corpus luteum]]. More detailed information regarding corpus luteum [[Corpus_Luteum_Formation_-_Anatomy_%26_Physiology|formation]] and [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|regression]] please use the links. Progesterone prepares the uterus for reception of fertilised oocytes and is transported via the blood bound to plasma proteins. Progesterone also prepares the mammary tissues for milk production as well as inhibiting female reproductive behaviours associated with oestrous.
 
 
The concentration of progesterone increases after ovulation increasing the growth of glands found in the endometrium resulting in increased secretion. These secretions include mucin, carbohydrates and specific proteins that are designed for nourishment of the embryo prior to implantation. Progesterone also stimulates the growth of the endometrium and stabilises smooth muscle cells to ensure that they do not contract during foetal development. Once near term, the concentration of progesterone decreases, altering the ratio between progesterone and oestrogen. This stimulates myometrial activity and prepares the uterus for parturition.
====Progesterone During Pregnancy====
During pregnancy the plasma concentration of progesterone is maintained at an elevated level. Progesterone also inhibits secretion of GnRH and also prevents the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Oestrus|ovulation]] of follicles during the [[Oestrous_Cycle_-_Anatomy_%26_Physiology#Luteal_Phase|luteal phase]] and during pregnancy. The exception to this rule is the mare in which the progesterone concentration falls during the later stages of pregnancy.
 
 
It is possible to use the relative concentration of progesterone as an aid to pregnancy diagnosis, for example in cattle. However, for a definitive diagnosis a high level of progesterone is required on two separate samples due to the overlap between the luteal phase and pregnancy.

===Testosterone (T)===
The male sex hormone is called testosterone and this hormone is required for [[Spermatogenesis_and_Spermiation_-_Anatomy_%26_Physiology|spermatogenesis]]. Testosterone is a steroid hormone that is produced in the leydig cells within the testes. A relatively high concentration of testosterone is maintained within the testicular tissue and testosterone is circulated around the body by diffusion of the hormone from the spermatic cord into the testicular veins and arteries. The primary action of testosterone is anabolic growth, spermatogenesis promotion and promotion of secretion from the accessory sex glands.
 
 
Male sex hormones are regulated by negative feedback systems that operate at various levels within the male sex hormone system. The starting point for the production of testosterone (and therefore the production of spermatozoa)is the hypothalamus. The hypothalamus contains neuroendocrine cells that are capable of secreting a substance called '''Gonadotropin-releasing hormone''' or GnRH. GnRH stimulates cells in the anterior pituitary, via the "portal system" to secrete two intermediate hormones within the male sex hormone cycle; '''Luteinizing hormone''' (LH) and '''Follicle-Stimulating Hormone''' (FSH).
 
 
The secretion of GnRH is pulsatile and can vary greatly throughout the day and/or year, and therefore the secretion of LH and FSH are also pulsatile (although the plasma concentration of FSH does not fluctuate as much as LH due to the effect of Inhibin, see below). The activity of GnRH neuroendocrine cells is determined by spontaneous rhythms and by sensory impulses. Cycles such as seasonal sexual activity are controlled by this pulsatile system. In male animals there are generally 4 to 12 GnRH pulses per day.
====Testosterone Regulation====
When LH binds to the Leydig cells, it stimulates the cellular messenger '''cAMP''' to '''activate protein kinase A'''. Protein kinase A undergoes a series of phosphorylations that in turn activate a series of enzymes that synthesis testosterone from the cholesterol base molecule. A portion of the testosterone produced in the Leydig cells diffuses into the Sertoli cells that are positioned adjacent to the Leydig cells in the testes but seperated by a basal lamina. This secreted testosterone is converted to to the female sex hormone estradiol in the Sertoli cell and as with the testosterone, a proportion diffuses into the blood, becoming part of the negative feedback system for LH.
 
 
Testosterone inhibits the secretion of GnRH from the hypothalamus and therefore secretion of LH from the pituitary gland. If the testes are removed via castration, blood concentrations of LH and FSH will increase as there is only limited negative feedback.

====Effects of Male Sex Hormones====
Testosterone plays a crucial role in the development of male sex organs during fetal growth where increased production of testosterone causes penis growth and development of accessory sex glands during puberty. Testosterone also affects a number of other characteristics of the male, often called the "secondary sex characteristics". Testosterone is able to bind to receptors in the cytosol of cells in the same manner as other steroid hormones and these hormone-receptor complexes are then able to bind to DNA in the nucleus resulting in alterations in the level of transcription of specific genes.
 
 
Testosterone has a number of anabolic effects stimulating the development and growth of the skeleton and skeletal muscles. Muscle masses show a general increase and in certain body regions such as the neck of stallions or bulls there is obvious hypertrophy. Testosterone also alters behaviour in terms of increasing the degree of sex drive and as a result of the action in several areas of the brain, behaviour can become more aggressive. The [[Larynx_-_Anatomy_%26_Physiology|larynx]] of males also enlarges during puberty and the vocal cords lengthen resulting in a deeper and stronger voice.
 
 
Testosterone also causes an increase in the level of pheromones to be secreted by glands in the skin which attract and evoke sexual behaviour in females. Glands use in scent marking and territorial marking are also activated by testosterone. In certain species, tusks, antlers and horns are also stimulated to develop.

===Inhibin===
Inhibin is a type of glycoprotein that is synthesised within the granulosa cells of ovarian follicles in females and in sertoli cells located in the seminiferous tubules within the testes in the male. In both males and females the target organ for inhibin is the anterior pituitary, specifically the gonadotroph cells.
 
 
In the male inhibin production is stimulated via androgens. Inhibin inhibits FSH secretion, which together with decreased concentrations of LH and testosterone results in decreased spermatogenesis and therefore decreased sperm output and quality.
 
 
In females some studies have suggested that inhibin may also be produced by the placenta. In females inhibin stimulates FSH secretion. When inhibin is secreted, a relatively higher concentration of LH is secreted from the anterior pituitary gland than FSH. Therefore during follicle development, the increased LH concentration causes cessation of the recruitment of further follicles under the effect of FSH. The hormonal changes resulting from the production of inhibin cause some of the previously recruited follicles to undergo atresia. Inhibin in the female can also be diminished by GnRH and enhanced by insulin-like growth factor-1 (IGF-1).

===Activin===
Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. Activin is thought to play an almost directly opposite role to that of inhibin and is involved in many physiological functions including stimulation of FSH synthesis and other roles including cell proliferation, cell differentiation, apoptosis and homeostasis.
 
 
The target tissue for activin in the male is the epididymis where it enhances spermatogenesis via increased FSH secretion. Activin also enhances the effect of LH on the testes.
 
 
In the female activin has an effect on the anterior pituitary gland, specifically on gonadotroph cells, resulting in increased FSH secretion. The increased concentrations of activin results in increased FSH binding on the female follicle and FSH-induced aromatisation (increased synthesis of oestrogens). Activin also enhances the action of LH in the ovary.
 
 
A further non-reproductive role of activin is it's role in skin lesions where it is thought to stimulate keratinocytes.

===Prostaglandin F2α===
Prostaglanin is a C2O fatty acid and is produced within the uterine endometrium and vesicular glands. Prostaglandins are lipid soluable and are therefore able to diffuse into the ovarian artery via veins that would otherwise take the PGF2α away from the uterine horn. The target tissue in the female is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]], uterine myometrium and ovulatory follicles. In the female prostaglandin can cause luteolysis and also cause the induction of tone and contractions within the uterus and ovulation.
 
 
During the latter stages of the luteal phase the corpus luteum begins to regress under the effect of PGF2α. Normally the concentration of PGF2α in arterial blood is relatively low due to extensive metabolism via the lungs. However there is a large concentration gradient from the uterine vein to the [[Ovary_-_Anatomy_%26_Physiology#Arterial_Supply|ovarian artery]] resulting in higher concentrations of PGF2α than in systemic circulation. If a pregnancy is to remain viable then luteolysis needs to be avoided and this is achieved where concentrations of PGF2α remain below a threshold level allowing the corpus luteum to continue to secrete prostaglandin. There are two main factors involved in the regulation of uterine secretions of PGF2α; oxytocin secretions from the corpus luteum and molecules secreted by the developing embryo that facilitate the maternal recognition of pregnancy.
 
 
Oxytocin secretion via the corpus luteum stimulates endometrial production of PGF2α and by the end of the luteal phase the concentration of oxytocin and the number of oxytocin recptors within the endometrium allow the production of enough PGF2α to breach the threshold level and cause luteolysis. During pregnancy the embryonically produced [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]] molecules inhibit the secretion of PGF2α from the endometrium ensuring that luteolysis cannot occur.

===Prostaglandin (PGE2)===
PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.
 
 
In females it's target tissue is the [[Corpus_Luteum_Regression_-_Anatomy_%26_Physiology|corpus luteum]] and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix and aids stimulation of uterine contractions.

===Human Chorionic Gonadotrophin (hCG)===
hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a [[Blastocyst_Embryonic_Development_-_Anatomy_%26_Physiology|blastocyst]]. hCG is particularly important in primate reproduction where it has a similar effect to LH in stimulating the continued production of progesterone and oestrogens. This represents part of the system involved in foetal-maternal communication and [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Primate blastocysts therefore produce hCG in relatively high concentrations during the first 3 months of pregnancy. hCG has also been suggested to play a role in defence of the embryo from the maternal immune system during the initial stages of pregnancy. In males hCG increases the growth of the foetal testes.
 
 
As hCG is only produced by embryonic cells, the presence of this hormone within maternal blood can be used for pregnancy confirmation.

===Equine Chorionic Gonadotrophin (eCG)===
eCG is a form of glycoprotein that is produced from chorionic girdle cells. Chorionic tissues in horses as well as primates also form hormones. eCG is formed in foetal endocrine cells and is found within the maternal circulation. eCG is thought to play a similar role in horses to hCG in primates in terms of [[Maternal_Recognition_of_Pregnancy_-_Anatomy_%26_Physiology|pregnancy recognition]]. Foetal production of eCG is highest between 30-70 days of pregnancy. The primary target of eCG are the ovaries where they faciliate the formation of the accessory corpora lutea and ensure that progesterone production is maintained.
 
 
eCG is also thought to stimulate follicular growth and ovulation in the horse. If eCG is given to other species it acts in a similar manner to FSH and therefore eCG is often used to induce super-ovulation in species where a large number of oocytes are required for embryo transfer.

===Placental Lactogen (PL)===
Placental lactogen is a form of protein that is produced by the placenta and is chemically close in composition to growth hormone. The primary target tissue of PL are the mammary glands where they stimulate the growth of alveoli during pregnancy.
 
 
PL is also referred to as Chorionic Somatomammotropin (CS).
===Relaxin===
Relaxin is produced in the placenta and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin is also responsible for the softening of connective tissues in the cervix and ligaments in the pelvis prior to parturition. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

{{OpenPages}}
[[Category:To Do - Review]]
[[Category:Reproductive System - Anatomy & Physiology]]

Reabsorption and Secretion Along the Proximal Tubule - Anatomy & Physiology

2013-11-01T23:54:44Z

ElzaTriegaardt: /* Sodium */

{{OpenPagesTop}}
==Introduction to Reabsorption==

* The [[Nephron Microscopic Anatomy #Proximal Tubule|proximal tubule]] is a major site for reabsorption and some secretion.
* Gradients are small across the epithelium so tight regulation is not possible
* This occurs in the [[Reabsorption and Secretion Along the Distal Tubule and Collecting Duct - Anatomy & Physiology#Distal Tubule| distal tubule]]
* 65-80% of the filtrate is reabsorbed
* Most reabsorption is coupled to sodium ion movement

* Small proteins and peptide hormones are reabsorbed by endocytosis
* Other substances are secreted or reabsorbed in the tubules passively by '''[[Transport Proteins - Physiology#Facilitated Diffusion |facilitated]]''', non-facilitated [[Diffusion - Physiology| '''diffusion''']] or [[Transport Proteins - Physiology#Diffusion Through Water Filled Protein Channels |'''ion channels''']] down chemical or electrical gradients.
* Other substances are secreted or reabsorbed by [[Active Transport - Physiology| '''active transport''']] against such gradients
** Movement is via [[Transport Proteins - Physiology#ATPases |'''ATPases''']].

* The reabsorbed material enters peritubular capillaries
* This is mainly driven by the Sodium/Pottasium ATPase in the basolateral membrane.
** This protein removes sodium from the cell maintaining the gradient between the lumen and the epithelium.
* Sodium reabsorption is driven by this protein
* Water and chloride then follow the transported sodium
* This is the most important transport mechanism in the proximal tubule

==Proportion of Filtered Substances Reabsorbed in the Proximal Tubule==

<TABLE CELLPADDING="2" CELLSPACING="2" WIDTH="40%">
<TR>
<TD BGCOLOR="#C1f0f6"><center>'''Substance'''</center></TD>
<TD BGCOLOR="#C1f0f6"><center>'''% of Filtrate Reabsorbed'''</center></TD>
</TR>
<TR>
<TD>Sodium and Water</TD>
<TD><center>~66%</center></TD>
</TR>
<TR>
<TD BGCOLOR="#C1f0f6">Organic solutes e.g. glucose and amino acids</TD>
<TD BGCOLOR="#C1f0f6"><center>~100%</center></TD>
</TR>
<TR>
<TD>Potassium</TD>
<TD><center>~65%</center></TD>
</TR>
<TR>
<TD BGCOLOR="#C1f0f6">Urea</TD>
<TD BGCOLOR="#C1f0f6"><center>~50%</center></TD>
</TR>
<TR>
<TD>Phosphate</TD>
<TD><center>~80%</center></TD>
</TR>
</TABLE>

==Epithelial Transport==

Sodium is the most important ion in relation to reabsorption from the proximal tubule. Water and chloride follow sodium passively and many other ions, compounds and molecules are absorbed through co-transporters with sodium. However it is vital that intracellular levels of sodium remain low to favour this reabsorption so it falls to the sodium/potassium ATPase and sodium pump to remove sodium from the cell. Also to a lesser extent active transport of protons (H+). As well as directly sodium linked transport secondary active transport also plays a part however this does tend to be powered by sodium movement. Passive transport also has a role

Transport capacity is well above what is needed for normal plasma concentrations to ensure that adequate absorption occurs and that there is little/no wastage. As sodium, chloride and water are reabsorbed at the same rate, the filtrate concentrations remains the same along the proximal tubule. Only the volume of the filtrate decreases.

==Ions and Compounds==
[[Image:sumabsproxtubtri.jpg|right|thumb|350px|<center>A summary of the reabsorption along the proximal tubule</center>]]
[[Image:NaKATPaseA+P.jpg|right|thumb|350px|<center>A sodium pottasium ATPase. (Courtesy of Phi-Gastrein)</center>]]
The following ions and compounds are reabsorbed or secreted partly or completely in the proximal tubule:

===Sodium===

The majority (70%) of sodium is reabsorbed in the [[Reabsorption and Secretion Along the Proximal Tubule - Anatomy & Physiology| proximal tubule.]] It is reabsorbed into the cytosol of the epithelial cells either alone by [[Diffusion - Physiology| diffusion]] through [[Transport Proteins - Physiology#Diffusion Through Water Filled Protein Channels|ion channels]] followed by water and chloride or together with another product such as glucose or AA using a [[Transport Proteins - Physiology#Co-Transporters|co-transporter]] by secondary active co-transport.

To maintain the concentration gradients and allow the diffusion to continue it is essential that sodium is not allowed to build up within the cell. This is the job of the sodium/potassium [[Transport Proteins - Physiology#ATPases|ATPase Pump]] and is an example of [[Active Transport - Physiology#Primary Active Transport|primary active transport]]. This pump removes three sodium ions from the cell and pumps two potassium ions back in. This creates a high concentration of potassium within the cell but this is corrected by potassium ion channels in the basolateral membrane which allow potassium to diffuse back into the interstitium. Because both sodium and potassium are leaving the cell the net effect is that the tubular cells are negatively charged. This creates an electro gradient which further increases sodium uptake from the cells. The combined electrochemical gradient is very large allowing for great amounts of sodium to be reabsorbed.

Sodium is then able to move from the interstial fluid into the blood due to the low hydrostatic pressure within the capillaries and a high protein osmotic pressure. These conditions are caused by the [[Glomerular Apparatus and Filtration - Anatomy & Physiology#Factors Which Determine Selective Filtration|selective filtration]] of water, ions and glucose but the selective obstruction of proteins and promote the reabsorption of water and the associated dissolved ions within it back into the blood.

===[[Aquaporins of the Kidney and Water Homeostasis - Anatomy & Physiology#The Ability of the Kidney To Alter the Water Content of the Body| Water]]===

===Potassium===

* Potassium is absorbed mainly by the paracellular route with water via osmosis
* Na+ / K+ ATPases in the basolateral membrane move potassium into epithelial cells from the interstitial spaces in order to remove sodium
* Potassium is then cleared from the cells using a co-transporter with chlorine
* No potassium excretion occurs here due to the lack of potassium ion channels in the apical membrane

===Urea===

50% of filtered urea is reabsorbed in the proximal tubule. However the concentration of urea actually increases thanks to the reabsorption of 70% of the filtered water in the same portion of the nephron. Urea is not able to be reabsorbed from this point until it reaches the lower portion of the collecting duct therefore its concentration further increases with the reabsorption of water.

===Glucose===
Glucose is a small molecule and so it is filtered in the same concentrations as are found in plasma which is approximately 5mmol/l. Reabsorption of glucose can only occur in the proximal tubule and occurs regardless of the concentration gradient as it is completed via [[Active Transport - Physiology#Secondary Active Transport|secondary active transport]]. It is reabsorbed using a [[Transport Proteins - Physiology#Co-Transporters|co-transporter]] with [[Essential Ion and Compound Balance and Homeostasis - Anatomy & Physiology#Sodium|sodium]]. The realisation of the [[Active Transport - Physiology#Development of Potential Energy|potential energy]] produced from sodium moving from an area of high concentration to an area of low concentration is enough energy to transport glucose across the membrane into the epithelial cells. The energy technically comes from the utilisation of ATP by the [http://w01.rvcwiki.wf.ulcc.ac.uk/images/e/ef/NaKATPaseA%2BP.jpg sodium/potassium] [[Transport Proteins - Physiology#ATPases|ATPase]] which keeps sodium concentrations within the epithelial cells low this giving the sodium in the lumen a high potential energy.

Glucose is then passively transported out of the epithelial cells across the basolateral membrane.

It is normal that reabsorption is fully completed in the first half of this tubule however as the plasma concentration of glucose increases more of the tubule will be utilised to reabsorb the glucose. Concentrations of double the normal levels are required for glucose to appear in the urine and the concentration where glucose can first be detected is termed the '''renal threshold for glucose'''.

=====T Max and Splay=====

At approximately three times the normal levels the kidneys begin to approach the maximum possible reabsorption levels this is termed '''Tmax''' and is where the entire length of all the proximal tubules of all the nephrons of the kidney are working at maximum capacity.

Prior to this point the amount of glucose excreted does not increase linearly with the amount filtered. This is because some nephrons have longer proximal tubules than others so although some may be overcome and therefore allowing glucose to be excreted others are managing to fully reabsorb the glucose along their length. This results in what is termed '''splay'''. However after '''Tmax''' all the nephrons are at and above full capacity and therefore after this point any increase in filtered glucose is demonstrated linearly with that excreted.

The '''Tmax''' for a 20Kg dog is approximately 170mg per minute or 220g per 24 hour period. The normal amount of glucose filtered in 24 hours should be 60g.

=====The Kidneys Role In Glucose Regulation=====

The kidneys do not really regulate plasma glucose but their main aim is to preserve this valuable nutrient. It is only at very high levels which the kidneys play a role in helping to prevent any further rises in glucose via excretion.

===The Secretion of H+ and the Reabsorption of HCO3-===
[[Image:acidbaseflowkidap1.jpg|right|thumb|350px|<center>Secretion of H+ and reabsorption of HCO3+ in the Proximal Tubule</center>]]

=====Secretion of H+=====
* The secretion of H+ in this section of the nephron is mainly a result of the Na+/H+ exchanger
** This is an antiporter in the apical membrane
** Energy for this process is provided by the Na/K ATPase in the basolateral membrane
** Therefore it is [[Active Transport - Physiology#Secondary Active Transport|secondary active transport]]
** The ATPase pumps sodium out of the cell into the interstitium
** This maintains a low intracellular Na which creates a gradient for the absorption of sodium by the Na+/H+ antiporter
** This allows it to drive H against its concentration gradient
** Maintains a negative intracellular potential
** It is essential that HCO3- is removed from the cells by the co-transporter with sodium to ensure efficient H+ secretion.

=====Reabsorption of HCO3-=====
* Very efficient reabsorption mechanism
* 90% in first 1-2mm of tubule
* Lots of luminal carbonic anhydrase
* Stops the accumulation of H2CO3 in the lumen
* Keeps H+ concentration low - helps antiporter
* Roles of '''carbonic anhydrase'''
** In the cell forms HCO3- from OH and CO2
** In the tubule it works in reverse forming CO2 and H2O from the intermediate H2CO3 which forms from HCO3- and H+
** Allows continuous H+ secretion and HCO3- reabsorption

===Protein===
Peptide hormones and small amounts of albumin make it through the [[Glomerular Apparatus and Filtration - Anatomy & Physiology#Function of Renal Corpuscle|glomerular filtration barrier]] and these need to be reabsorbed. The reabsorption occurs via '''endocytosis''' in the proximal tubules. They are then broken down to amino acids in the epithelial cell cytoplasm and move via facilitated diffusion into the interstial fluid. The reabsorption of protein is usually complete though it is normal to detect small quantities of protein in the urine of some mammals e.g. the dog

===Primary Active Secretion - Organic Acids and Bases===
The secretion of these compounds occurs '''only in the proximal tubules'''. These molecules are mainly bound to plasma proteins with a small amount free in an active ionised form. It is only the free ions which are able to be transported. As the ionised molecules are transported out of the blood more molecules are ionised from the plasma proteins to take their place. These new ionised molecules are then able to be excreted thus releasing more and so it goes on. This allows a large amount of the substance to be secreted at one time. The mechanisms are not very selective and so many different substances are secreted at the same time. Secretion mechanisms are responsible for the secretion of drugs, hormones and things like food additives. Many unwanted or toxic organic molecules which enter the body are unionized. They therefore cannot be secreted so it falls to the liver to alter them into ionized forms to allow them to be disposed of.

===[[Calcium|Calcium]]===
Half the plasma calcium is bound to proteins so it is only the ionised form which is available for filtration. Reabsorption of calcium occurs in the proximal tubule paracellulary however the regulation of how much is reabsorbed occurs in the ascending limb of the loop of henle, the distal tubule and collecting ducts.

==Revision==

Use the [[Reabsorption and Secretion Along the Proximal Tubule - Renal Flash Cards - Anatomy & Physiology|flash card revision resource]] for this section to test yourself.

{{OpenPages}}
[[Category:Urine Production]]
[[Category:Bullet Points]]

Nephron Microscopic Anatomy

2013-11-01T23:35:08Z

ElzaTriegaardt: /* The Bowmans Capsule */

{{OpenPagesTop}}
==The Renal Corpuscle==
===Glomerulus===
[[Image:normcorpusclekidapx.jpg|right|thumb|250px|<center>Histology section of a normal renal corpuscle (© RVC 2008)</center>]]
[[Image:normcorpusclekidap2.jpg|right|thumb|250px|<center>Histology section of a normal renal corpuscle (© RVC 2008)</center>]]
[[Image:normcorpusclebowmankidap.jpg|right|thumb|250px|<center>Histology section of a normal renal corpuscle showing the layers of the bowmans capsule (© RVC 2008)</center>]]
[[Image:proxdisttub.jpg|right|thumb|250px|<center>Histology section of renal tubules (© RVC 2008)</center>]]
[[Image:collductloh.jpg|right|thumb|250px|<center>Histology section of the collecting duct showing the close proximity of the loop of henle (© RVC 2008)</center>]]
[[Image:collduct.jpg|right|thumb|250px|<center>Histology section of the collecting duct (© RVC 2008)</center>]]
* Made up of many parallel capillaries
* These capillaries do not connect to venules as with other capillaries
* Blood flows into these capillaries through a wide afferent arteriole and leaves through a narrower efferent arteriole
* The flow from the efferant arteriole enters the [[Glomerular Apparatus and Filtration - Anatomy & Physiology#Pressure in the Peritubular Capillaries|peritubular capillaries]] surrounding the proximal tubule
* This change in diameter maintains a high filtration pressure which is essential for filtration
* Also the blood entering the afferent arteriole is at very high pressure already as it from the renal artery
* The pressure actually forces molecules through the [[Glomerular Apparatus and Filtration - Anatomy & Physiology#Glomerular Filtration|'''glomerular filtration barrier''']] which is responsible for selectively filtering the blood forming the glomerular filtrate.
* As well as the the cells in the blood vessels the other component of the glomerulus are the mesangial cells:
** These give support to the glomerulus
** Maintain glomerular basal lamina

===The Bowmans Capsule===

* Surrounds the capillaries of the glomerulus
* Has two layers separated by the '''urinary space'''
** Inner visceral layer - Podocytes
** Outer parietal layer
* It is here where the filtrate is collected before entering the proximal tubule

===The Physiology of the Renal Corpuscle===

Details of the physiology of the renal corpuscle can be found [[Glomerular Apparatus and Filtration - Anatomy & Physiology#Glomerular Filtration|here]]

==Proximal Tubule==
* This is the piece of nephron which starts at the Bowmans capsule and ends in the loop of henle
* Consists of two parts which differ in cell morphology and function
** Pars convoluter - joins the urinary pole of the Bowmans capsule
** Pars recta (straight part) - links the pars convoluter to the descending thin limb of the loop of henle
* Has a brush border of densely packed microvilli to increase surface area
* The basal lamina is striated to increase the surface area for reabsorption
** Typical of actively ion transporting epithelial cells
** Lots of mitochondria to provide energy for exchange
** Lots of Na+ / K+ ATPases to maintain ion levels in cells at right level to allow efficient take up of ions from lumen

===The Physiology of the Proximal Tubule===
Details of the physiology of the proximal tubule can be found [[Reabsorption and Secretion Along the Proximal Tubule - Anatomy & Physiology|here]]

==The Loop of Henle==

The loop of henle basically consists of two parallel limbs which descend from the cortex into the medulla. They are joined at the bottom and as such the flow moves down one limb and up the other in opposite directions. This sets up a counter current exchange and allows the loop of henle to be the major site of water reabsorption along the nephron. It has three parts; the thin decsending limb, the thin ascending limb and the thick ascending limb

===The Physiology of the Loop of Henle===

Details of the physiology of the loop of henle can be found [[Reabsorption and Secretion Along the Loop of Henle - Anatomy & Physiology|here]]

==The Distal Tubule==

* Consists of two parts
** Straight part - connects the thick ascending limb of the loop of henle to the convoluted distal tubule
** Convoluted part - connects the straight part to the connecting duct
* No brush border - very few micro villi (compared to the proximal tubule)
* The basal lamina is striated to increase the surface area for reabsorption

===The Physiology of the Distal Tubule===

Details of the physiology of the distal tubule can be found [[Reabsorption and Secretion Along the Distal Tubule and Collecting Duct - Anatomy & Physiology#Distal Tubule|here]]

==Collecting Duct==

* This structure links the distal tubule to the area cribosa of the papilla into the renal pelvis
* Here the final concentration of the urine occurs as the collecting duct makes the transition from the isotonic cortex to the hypertonic medulla the increasing osmolarity of the interstial fluid causes more and more water to be reabsorbed.
* The collecting duct has 2 cell types
** Intercalated cells
** Principal cells
* The cells are flat to cylindrical
* Have clearly visible cell borders

===The Physiology of the Collecting Duct===

Details of the physiology of the collecting duct can be found [[Reabsorption and Secretion Along the Distal Tubule and Collecting Duct - Anatomy & Physiology#Collecting Duct|here]]

==Blood Supply to the Nephron==

The blood enters the glomerulus through the afferent arteriole. It is filtered by the glomerulus and what remains in the blood vessels leaves this structure via the efferent arteriole. The vessel then winds around the proximal tubule and is thus called a peritubular capillary. As it works its way along the tubule it collects the reabsorbed substances which it originally lost in the glomerulus. As the tubule descends into the medulla and becomes the Loop of Henle the blood vessel follows it and becomes what is known as the vasa recta. Upon its exit from the the medulla it wraps itself around the distal tubule.

===The Vasa Recta===

Vasa Recta is the name given to blood vessels supplying the medullary region of the kidney. They are arranged in a U configuration but flow is opposite to that of the [[Reabsorption and Secretion Along the Loop of Henle - Anatomy & Physiology| Loop of Henle]]. The blood vessels descend from the cortex down into the medulla. It supplies the nutrients and oxygen the [[Reabsorption and Secretion Along the Loop of Henle - Anatomy & Physiology| Loop of Henle]] needs.

The physiology of the vasa recta can be found [[Reabsorption and Secretion Along the Loop of Henle - Anatomy & Physiology#Vasa Recta Physiology|here]]

==Revision==

Use the [[Microscopic Anatomy of the Nephron - Renal Flash Cards - Anatomy & Physiology|flash card revision resource]] for this section to test yourself.

{{OpenPages}}
[[Category:Nephron]]
[[Category:Bullet Points]]

Renin Angiotensin Aldosterone System

2013-11-01T23:14:04Z

ElzaTriegaardt: /* Effects of Angiotensin II on Blood Pressure */

{{OpenPagesTop}}
Also known as: '''''RAAS'''''

[[Image:RAS.jpg|right|thumb|300px|<center> Schematic of the RAAS ©RVC 2008</center>]]

==Introduction==

The RAAS is activated whenever blood flow through the kidneys is reduced, and when there are sodium losses in conditions such as diarrhoea, vomiting or excessive sweating. These losses reduce extracellular fluid volume, and this in turn reduces arterial blood pressure, which triggers the RAAS system through several different mechanisms.

==RAAS Activation==

[[Image:raasflowdefap.jpg|right|thumb|275px|<center>The Mechanism Behind the RAAS </center>]]
[[Image:raasflowsumap.jpg|right|thumb|250px|<center>Summary of the purpose of the RAAS</center>]]

In the event of blood pressure dropping, [[Kidney Endocrine Function - Anatomy & Physiology#Renin|renin]] is secreted due to the decreased stretch of the [[Reabsorption and Secretion Along the Distal Tubule and Collecting Duct - Anatomy & Physiology#Juxtaglomerular Cells|'''juxtaglomerular cells''']] and an increased sympathetic stimulation, triggered by the decreased activation of arterial baroreceptors. This enzyme cleaves the alpha glycoprotein, '''angiotensinogen''', which is released from the [[Liver - Anatomy & Physiology|liver]]. This produces '''angiotensin 1''', which is further converted by [[Angiotensin Converting Enzyme|'''Angiotensin Converting Enzyme''' (ACE)]] to '''angiotensin II''', mainly in the lungs but to a much lesser extent locally in the kidneys. Angiotensin II then works to restore blood pressure by inducing constriction of peripheral vessels (arterioles), which increases vascular resistance, and constricting veins which reduces vascular volume. In this section, we cover its effects on and through the kidneys.

==Effects of Angiotensin II on Blood Pressure==

'''Angiotensin II''' acts on '''AT1 receptors''' to stimulate the release of '''[[Aldosterone|aldosterone]]''' from the [[Adrenal Glands - Anatomy & Physiology#Adrenal Glands|zona glomerulosa]] of the adrenal glands. This mineralocorticoid increases the excretion of potassium and the reabsorption of sodium, and therefore water and chloride from the distal tubule of the kidney, thus helping to increase blood pressure and volume. It also stimulates the thirst center, and increases the secretion of [[Pituitary Gland - Anatomy & Physiology #Posterior Pituitary Gland |anti-diuretic hormone (ADH)]] to help increase blood volume by making the distal convoluted tubule and the collecting duct permeable to water. The RAAS allows pressure to return to 50% of baseline within 15 minutes of a significant haemorrhage occurring.

==Effects of Angiotensin II on GFR==

If blood pressure drops then [[Glomerular Apparatus and Filtration - Anatomy & Physiology#Glomerular Filtration Rate|glomerular filtration rate (GFR)]] also drops, due to reduced blood flow through the kidneys. To restore homeostasis, contraction of the efferent arteriole occurs in response to angiotensin II and the pressure difference between the afferent and efferent arterioles increases, creating greater filtration pressure. Therefore, when blood pressure falls, there is minimum alteration of GFR. The increased renal resistance to blood flow and the maintained GFR has many advantageous effects.

===Advantages of Angiotensin II induced Vasoconstriction===

Increased total peripheral resistance helps to return blood pressure towards normal. (Angiotensin II also has vasoconstrictive effects in multiple organs.) The reduced perfusion of the kidneys allows blood to be diverted to the brain and heart. The constriction of the efferent arterioles also reduces hydrostatic pressure in the [[Glomerular Apparatus and Filtration - Anatomy & Physiology#Pressure in the Peritubular Capillaries|peritubular capillaries]], increasing reabsorption of water and salt and helping to restore the extracellular fluid (ECF) and normalising blood pressure. The amount of waste excreted is linked to the GFR. Maintaining GFR, permits the excretion of waste products such as urea to be maintained.

==Effects of Angiotensin II On Sodium==

Induces insertion of Na+ channels into renal tubules via stimulation of AT1 receptors. These occur in:

1. The proximal tubule, with the addition of:

Apical - Na+/H+ exchangers and basolateral Na+(HCO3-)3 and Na+K+ATPase.

2. The thick ascending limb, with the addition of:

Apical Na+/H+ exchangers and Na+K+2Cl- symporter.

3. The collecting ducts, with the addition of:

Epithelial Na+ channels.

Angiotensin II also stimulates the release of '''Aldosterone'''.

{{Template:Learning
|flashcards = [[Important Hormonal Regulators of the Kidney - Renal Flash Cards - Anatomy & Physiology|Hormonal Regulators of the Kidney]]
}}

{{OpenPages}}
[[Category:Kidney Hormonal Regulators]][[Category:Endocrine System - Anatomy & Physiology]]
[[Category:Blood Pressure]]
[[Category:A&P Done]]
[[Category:Cardiology Section]]

Renin Angiotensin Aldosterone System

2013-11-01T23:11:12Z

ElzaTriegaardt: /* Effects of Angiotensin II on Blood Pressure */

{{OpenPagesTop}}
Also known as: '''''RAAS'''''

[[Image:RAS.jpg|right|thumb|300px|<center> Schematic of the RAAS ©RVC 2008</center>]]

==Introduction==

The RAAS is activated whenever blood flow through the kidneys is reduced, and when there are sodium losses in conditions such as diarrhoea, vomiting or excessive sweating. These losses reduce extracellular fluid volume, and this in turn reduces arterial blood pressure, which triggers the RAAS system through several different mechanisms.

==RAAS Activation==

[[Image:raasflowdefap.jpg|right|thumb|275px|<center>The Mechanism Behind the RAAS </center>]]
[[Image:raasflowsumap.jpg|right|thumb|250px|<center>Summary of the purpose of the RAAS</center>]]

In the event of blood pressure dropping, [[Kidney Endocrine Function - Anatomy & Physiology#Renin|renin]] is secreted due to the decreased stretch of the [[Reabsorption and Secretion Along the Distal Tubule and Collecting Duct - Anatomy & Physiology#Juxtaglomerular Cells|'''juxtaglomerular cells''']] and an increased sympathetic stimulation, triggered by the decreased activation of arterial baroreceptors. This enzyme cleaves the alpha glycoprotein, '''angiotensinogen''', which is released from the [[Liver - Anatomy & Physiology|liver]]. This produces '''angiotensin 1''', which is further converted by [[Angiotensin Converting Enzyme|'''Angiotensin Converting Enzyme''' (ACE)]] to '''angiotensin II''', mainly in the lungs but to a much lesser extent locally in the kidneys. Angiotensin II then works to restore blood pressure by inducing constriction of peripheral vessels (arterioles), which increases vascular resistance, and constricting veins which reduces vascular volume. In this section, we cover its effects on and through the kidneys.

==Effects of Angiotensin II on Blood Pressure==

'''Angiotensin II''' acts on '''AT1 receptors''' to stimulate the release of '''[[Aldosterone|aldosterone]]''' from the [[Adrenal Glands - Anatomy & Physiology#Adrenal Glands|zona glomerulosa]] of the adrenal glands. This mineralocorticoid increases the excretion of potassium and the reabsorption of sodium, and therefore water and chloride from the distal tubule of the kidney, thus helping to increase blood pressure and volume. It also stimulates the thirst center, and increases the secretion of [[Pituitary Gland - Anatomy & Physiology #Posterior Pituitary Gland |anti-diuretic hormone (ADH)]] to help increase blood volume. The RAAS allows pressure to return to 50% of baseline within 15 minutes of a significant haemorrhage occurring.

==Effects of Angiotensin II on GFR==

If blood pressure drops then [[Glomerular Apparatus and Filtration - Anatomy & Physiology#Glomerular Filtration Rate|glomerular filtration rate (GFR)]] also drops, due to reduced blood flow through the kidneys. To restore homeostasis, contraction of the efferent arteriole occurs in response to angiotensin II and the pressure difference between the afferent and efferent arterioles increases, creating greater filtration pressure. Therefore, when blood pressure falls, there is minimum alteration of GFR. The increased renal resistance to blood flow and the maintained GFR has many advantageous effects.

===Advantages of Angiotensin II induced Vasoconstriction===

Increased total peripheral resistance helps to return blood pressure towards normal. (Angiotensin II also has vasoconstrictive effects in multiple organs.) The reduced perfusion of the kidneys allows blood to be diverted to the brain and heart. The constriction of the efferent arterioles also reduces hydrostatic pressure in the [[Glomerular Apparatus and Filtration - Anatomy & Physiology#Pressure in the Peritubular Capillaries|peritubular capillaries]], increasing reabsorption of water and salt and helping to restore the extracellular fluid (ECF) and normalising blood pressure. The amount of waste excreted is linked to the GFR. Maintaining GFR, permits the excretion of waste products such as urea to be maintained.

==Effects of Angiotensin II On Sodium==

Induces insertion of Na+ channels into renal tubules via stimulation of AT1 receptors. These occur in:

1. The proximal tubule, with the addition of:

Apical - Na+/H+ exchangers and basolateral Na+(HCO3-)3 and Na+K+ATPase.

2. The thick ascending limb, with the addition of:

Apical Na+/H+ exchangers and Na+K+2Cl- symporter.

3. The collecting ducts, with the addition of:

Epithelial Na+ channels.

Angiotensin II also stimulates the release of '''Aldosterone'''.

{{Template:Learning
|flashcards = [[Important Hormonal Regulators of the Kidney - Renal Flash Cards - Anatomy & Physiology|Hormonal Regulators of the Kidney]]
}}

{{OpenPages}}
[[Category:Kidney Hormonal Regulators]][[Category:Endocrine System - Anatomy & Physiology]]
[[Category:Blood Pressure]]
[[Category:A&P Done]]
[[Category:Cardiology Section]]

Renin Angiotensin Aldosterone System

2013-11-01T23:07:04Z

ElzaTriegaardt: /* RAAS Activation */

{{OpenPagesTop}}
Also known as: '''''RAAS'''''

[[Image:RAS.jpg|right|thumb|300px|<center> Schematic of the RAAS ©RVC 2008</center>]]

==Introduction==

The RAAS is activated whenever blood flow through the kidneys is reduced, and when there are sodium losses in conditions such as diarrhoea, vomiting or excessive sweating. These losses reduce extracellular fluid volume, and this in turn reduces arterial blood pressure, which triggers the RAAS system through several different mechanisms.

==RAAS Activation==

[[Image:raasflowdefap.jpg|right|thumb|275px|<center>The Mechanism Behind the RAAS </center>]]
[[Image:raasflowsumap.jpg|right|thumb|250px|<center>Summary of the purpose of the RAAS</center>]]

In the event of blood pressure dropping, [[Kidney Endocrine Function - Anatomy & Physiology#Renin|renin]] is secreted due to the decreased stretch of the [[Reabsorption and Secretion Along the Distal Tubule and Collecting Duct - Anatomy & Physiology#Juxtaglomerular Cells|'''juxtaglomerular cells''']] and an increased sympathetic stimulation, triggered by the decreased activation of arterial baroreceptors. This enzyme cleaves the alpha glycoprotein, '''angiotensinogen''', which is released from the [[Liver - Anatomy & Physiology|liver]]. This produces '''angiotensin 1''', which is further converted by [[Angiotensin Converting Enzyme|'''Angiotensin Converting Enzyme''' (ACE)]] to '''angiotensin II''', mainly in the lungs but to a much lesser extent locally in the kidneys. Angiotensin II then works to restore blood pressure by inducing constriction of peripheral vessels (arterioles), which increases vascular resistance, and constricting veins which reduces vascular volume. In this section, we cover its effects on and through the kidneys.

==Effects of Angiotensin II on Blood Pressure==

'''Angiotensin II''' acts on '''AT1 receptors''' to stimulate the release of '''[[Aldosterone|aldosterone]]''' from the [[Adrenal Glands - Anatomy & Physiology#Adrenal Glands|zona glomerulosa]] of the adrenal glands. This mineralocorticoid increases the reabsorption of sodium, and therefore water and chloride from the distal tubule of the kidney, thus helping to increase blood pressure and volume. It also stimulates the thirst center, and increases the secretion of [[Pituitary Gland - Anatomy & Physiology #Posterior Pituitary Gland |anti-diuretic hormone (ADH)]] to help increase blood volume. The RAAS allows pressure to return to 50% of baseline within 15 minutes of a significant haemorrhage occurring.

==Effects of Angiotensin II on GFR==

If blood pressure drops then [[Glomerular Apparatus and Filtration - Anatomy & Physiology#Glomerular Filtration Rate|glomerular filtration rate (GFR)]] also drops, due to reduced blood flow through the kidneys. To restore homeostasis, contraction of the efferent arteriole occurs in response to angiotensin II and the pressure difference between the afferent and efferent arterioles increases, creating greater filtration pressure. Therefore, when blood pressure falls, there is minimum alteration of GFR. The increased renal resistance to blood flow and the maintained GFR has many advantageous effects.

===Advantages of Angiotensin II induced Vasoconstriction===

Increased total peripheral resistance helps to return blood pressure towards normal. (Angiotensin II also has vasoconstrictive effects in multiple organs.) The reduced perfusion of the kidneys allows blood to be diverted to the brain and heart. The constriction of the efferent arterioles also reduces hydrostatic pressure in the [[Glomerular Apparatus and Filtration - Anatomy & Physiology#Pressure in the Peritubular Capillaries|peritubular capillaries]], increasing reabsorption of water and salt and helping to restore the extracellular fluid (ECF) and normalising blood pressure. The amount of waste excreted is linked to the GFR. Maintaining GFR, permits the excretion of waste products such as urea to be maintained.

==Effects of Angiotensin II On Sodium==

Induces insertion of Na+ channels into renal tubules via stimulation of AT1 receptors. These occur in:

1. The proximal tubule, with the addition of:

Apical - Na+/H+ exchangers and basolateral Na+(HCO3-)3 and Na+K+ATPase.

2. The thick ascending limb, with the addition of:

Apical Na+/H+ exchangers and Na+K+2Cl- symporter.

3. The collecting ducts, with the addition of:

Epithelial Na+ channels.

Angiotensin II also stimulates the release of '''Aldosterone'''.

{{Template:Learning
|flashcards = [[Important Hormonal Regulators of the Kidney - Renal Flash Cards - Anatomy & Physiology|Hormonal Regulators of the Kidney]]
}}

{{OpenPages}}
[[Category:Kidney Hormonal Regulators]][[Category:Endocrine System - Anatomy & Physiology]]
[[Category:Blood Pressure]]
[[Category:A&P Done]]
[[Category:Cardiology Section]]

Renin Angiotensin Aldosterone System

2013-11-01T23:06:16Z

ElzaTriegaardt: /* RAAS Activation */

{{OpenPagesTop}}
Also known as: '''''RAAS'''''

[[Image:RAS.jpg|right|thumb|300px|<center> Schematic of the RAAS ©RVC 2008</center>]]

==Introduction==

The RAAS is activated whenever blood flow through the kidneys is reduced, and when there are sodium losses in conditions such as diarrhoea, vomiting or excessive sweating. These losses reduce extracellular fluid volume, and this in turn reduces arterial blood pressure, which triggers the RAAS system through several different mechanisms.

==RAAS Activation==

[[Image:raasflowdefap.jpg|right|thumb|275px|<center>The Mechanism Behind the RAAS </center>]]
[[Image:raasflowsumap.jpg|right|thumb|250px|<center>Summary of the purpose of the RAAS</center>]]

In the event of blood pressure dropping, [[Kidney Endocrine Function - Anatomy & Physiology#Renin|renin]] is secreted due to the decreased stretch of the [[Reabsorption and Secretion Along the Distal Tubule and Collecting Duct - Anatomy & Physiology#Juxtaglomerular Cells|'''juxtaglomerular cells''']] and an increased sympathetic stimulation, triggered by the decreased activation of arterial baroreceptors. This enzyme cleaves the alpha glycoprotein, '''angiotensinogen''', which is released from the [[Liver - Anatomy & Physiology|liver]]. This produces '''angiotensin 1''', which is further converted by [[Angiotensin Converting Enzyme|'''Angiotensin Converting Enzyme''' (ACE)]] to '''angiotensin II''', mainly in the lungs but to a much lesser extent locally in the kidneys. Angiotensin II then works to restore blood pressure by inducing constriction of peripheral vessels (arterioles), which increases vascular resistance, and constricting veins which reduces vascular volume. In this section, we cover its effects on and through the kidneys.t

==Effects of Angiotensin II on Blood Pressure==

'''Angiotensin II''' acts on '''AT1 receptors''' to stimulate the release of '''[[Aldosterone|aldosterone]]''' from the [[Adrenal Glands - Anatomy & Physiology#Adrenal Glands|zona glomerulosa]] of the adrenal glands. This mineralocorticoid increases the reabsorption of sodium, and therefore water and chloride from the distal tubule of the kidney, thus helping to increase blood pressure and volume. It also stimulates the thirst center, and increases the secretion of [[Pituitary Gland - Anatomy & Physiology #Posterior Pituitary Gland |anti-diuretic hormone (ADH)]] to help increase blood volume. The RAAS allows pressure to return to 50% of baseline within 15 minutes of a significant haemorrhage occurring.

==Effects of Angiotensin II on GFR==

If blood pressure drops then [[Glomerular Apparatus and Filtration - Anatomy & Physiology#Glomerular Filtration Rate|glomerular filtration rate (GFR)]] also drops, due to reduced blood flow through the kidneys. To restore homeostasis, contraction of the efferent arteriole occurs in response to angiotensin II and the pressure difference between the afferent and efferent arterioles increases, creating greater filtration pressure. Therefore, when blood pressure falls, there is minimum alteration of GFR. The increased renal resistance to blood flow and the maintained GFR has many advantageous effects.

===Advantages of Angiotensin II induced Vasoconstriction===

Increased total peripheral resistance helps to return blood pressure towards normal. (Angiotensin II also has vasoconstrictive effects in multiple organs.) The reduced perfusion of the kidneys allows blood to be diverted to the brain and heart. The constriction of the efferent arterioles also reduces hydrostatic pressure in the [[Glomerular Apparatus and Filtration - Anatomy & Physiology#Pressure in the Peritubular Capillaries|peritubular capillaries]], increasing reabsorption of water and salt and helping to restore the extracellular fluid (ECF) and normalising blood pressure. The amount of waste excreted is linked to the GFR. Maintaining GFR, permits the excretion of waste products such as urea to be maintained.

==Effects of Angiotensin II On Sodium==

Induces insertion of Na+ channels into renal tubules via stimulation of AT1 receptors. These occur in:

1. The proximal tubule, with the addition of:

Apical - Na+/H+ exchangers and basolateral Na+(HCO3-)3 and Na+K+ATPase.

2. The thick ascending limb, with the addition of:

Apical Na+/H+ exchangers and Na+K+2Cl- symporter.

3. The collecting ducts, with the addition of:

Epithelial Na+ channels.

Angiotensin II also stimulates the release of '''Aldosterone'''.

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[[Category:Kidney Hormonal Regulators]][[Category:Endocrine System - Anatomy & Physiology]]
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