Puberty Endocrine Events - Anatomy & Physiology

Hypothalamic Neuron Release of GnRH

• Hypothalamic development occurs gradually with growth of the animal.

Female

• The Hypothalamus contains a tonic GnRH centre and a preovulatory GnRH 'surge' centre.
• Before puberty can occur, full neural activity of the surge centre must be achieved.
• GnRH neurons must fire frequently and release large quantities of GnRH in order to cause the pre-ovulatory LH surge.
• The pre-ovulatory LH surge is a series of rapid, high amplitude pulses.
• Inability of the surge centre to function will result in failure to ovulate.
• In addition to the surge centre in the female, at puberty the tonic centre must also reach a functional state.
• The tonic centre regulates the tonic frequency of GnRH pulses.

• The pre-pubertal female has a lack of gonadal oestradiol to stimulate the surge centre.
• The tonic GnRH centre stimulates LH pulses from the Anterior Pituitary Gland. The amplitude of these pulses is the same as in the post-pubertal female, but the frequency is much lower.
• Prior to puberty, low frequency GnRH pulses do not provide enough stimulus for the Anterior Pituitary Gland to release FSH and LH at high levels.
• Therefore, follicular development does not result in high levels of circulating oestradiol.
• Oestradiol remains below the threshold that is needed to trigger the GnRH surge centre.
• The secretion of GnRH from the surge centre neurons is controlled by both positive and negative feedback.
• Puberty is initiated when GnRH neurons can respond completely to the positive and negative feedback.
• The surge centre and the tonic centre in the Hypothalamus are anatomically distinct from one another.
• The surge centre responds primarily to positive feedback stimulus.
• In the pre-pubertal female, the sensitivity of the surge centre to the positive feedback of oestrogen is quite high, but ovulation does not occur. This is because the immature ovaries do not produce enough oestrogen to activate the highly sensitive surge centre.
• At these low levels of oestrogen, the tonic centre has high sensitivity to negative feedback stimulus, therefore it does not produce high levels of GnRH so LH and FSH levels also remain low.
• During the approach to puberty, the sensitivity of the tonic centre to negative feedback decreases, allowing increasing amounts of GnRH to be produced.
• Increased amounts of GnRH lead to increased LH and FSH, which results in higher oestrogen production by the ovaries.
• When oestrogen levels reach a certain threshold, the surge centre is triggered by positive feedback. This results in a massive discharge of GnRH.
• This causes a surge in LH, so ovulation can occur and puberty ensues.
• The sensitivity of the surge centre never changes. Puberty is triggered because the sensitivity of the tonic centre to negative feedback decreases. This allows smaller quantities of oestrogen to stimulate the release of GnRH and thus LH and FSH. These gonadotrophins then stimulate follicles, so that more and more oestrogen is produced until it is sufficient to trigger the surge centre to release the pre-ovulatory surge of GnRH.

Male

• Does not develop a surge centre.
• The feedback system after puberty is a simple negative feedback loop.
• The negative feedback effect on GnRH is mainly due to some testosterone and mostly due to oestradiol because most testosterone is converted to oestradiol within the brain by aromatization.
• GnRH neurons become increasingly less sensitive to the negative feedback of testosterone and oestradiol as puberty approaches.
• Larger and larger quantities of testosterone and oestradiol are needed to inhibit the GnRH neurons.
• Thus, there is decreased sensitivity to the negative feedback of testosterone/oestrodiol.
• Therefore, the hypothalamus can produce increasing amounts of GnRH.
• Thus, more LH and FSH are produced until puberty is reached.

The Influence of Blood Glucose and Fatty Acids

• There are three types of presynaptic neurons that can stimulate GnRH neurons:
  • Leptin sensitive neurons
  • Glucose sensitive neurons
  • Fatty acid sensitive neurons

Leptin

• Leptin is a hormonal peptide produced by adipocytes (fat cells).
• The amount of leptin in the blood is directly related to the amount of fat in the body.
• Leptin receptors are found in the liver, kidney, heart, skeletal muscles, pancreas, anterior pituitary gland and hypothalamus.
• Leptin may be a signal that notifies GnRH neurons directly that nutritional status is adequate because a threshold 'fatness' has been achieved. Leptin may also signal to GnRH neurons indirectly via stimulation of neuropeptide Y, which in turn stimulates GnRH neurons.

Glucose

• Blood glucose stimulate glucose sensing neurons.
• Glucose sensing neurons stimulate GnRH neurons to produce GnRH.

Blood Fatty Acids

• Blood fatty acids stimulate neurons that in turn stimulate GnRH neurons.
• Blood fatty acids are an indicator of nutritional status.