Reproductive Hormones Overview - Anatomy & Physiology

Introduction

Reproductive hormones often have multiple roles and operate via negative feedback systems. The information below will provide the main reproductive hormones in domestic species and their functions.

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.

GnRH in Males

In males there are between 4-12 GnRH peaks per day. Plasma concentrations of LH peak approximately 10mins post GnRH surge.

Leutinising Hormone (LH)

LH is a type of glycoprotein that is produced in the Anterior Pituitary via gonadotroph cells. Their target tissue in the male are Leydig cells in the testes and in the female their target are Theca interna cells and luteal cells within the ovary. In the male LH stimulates testosterone production whilst in the female it stimulates ovulation and the formation of the corpora lutea together with progesterone secretion.

Follicle Stimulating Hormone (FSH)

FSH is a type of glycoprotein that is produced in the Anterior Pituitary via gonadotroph cells. Their target tissue in males are Sertoli cells within the testes and in the female Granulosa cells of the ovary. In the male FSH stimulates the secretion of inhibin which has a negative feedback directly in the anterior pituitary, whilst in the female it stimulates follicular development and oestradiol synthesis.

Prolactin (PRL)

PRL is a protein that is produced from the Anterior Pituitary via lactotroph cells. In males the target tissues are the testes and the brain whilst in females the target tissue are cells located within the mammary tissues and the corpus luteum in rodents. In the male PRL induces maternal behaviour whilst it also does this in the female together with lactation and ensuring functionality of the corpora lutea in some species.

Oxytocin (OT)

OT is a neuropeptide (a octapeptide) which is synthesised in the hypothalamus and stored in the posterior pituitary. OT can also be synthesised by the corpus luteum. In males the target tissue for OT is smooth muscle within the epididymal tail, ductus deferens and the ampulla. In females OT targets the uterine myometrium and endometrium together with cells of the mammary glands. In the male OT stimulates PGF2α synthesis and facilitates the pre-ejaculatory movement of spermatozoa. In females, OT stimulates uterine motility and the synthesis of PGF2α from the uterus. It also begins milk 'let-down' or ejection.

Oestradiol (E₂)

E₂ is a steroid that is produced by the granulosa cells of a follicle, the placenta and the testes. In males the target tissue is the brain for maturation of the male brain during foetal development. E₂ in the male also inhibits long bone growth. In females the target tissues are the hypothalamus, the entire female reproductive tract and the mammary glands. The primary action of E₂ in males is the appropriate development of male sexual behaviours whilst in females it influences sexual behaviour, GnRH levels, the secretory activity of the reproductive tract and enhances uterine motility.

Progesterone (P₄)

Progesterone is a steroid hormone that is produced by the corpus luteum and the placenta. In males the target tissues are the accessory sex glands, the tunica dartos (scrotum), the seminiferous tubules and skeletal muscles. In females the target tissues are the uterine endometrium, the mammary gland, the myometrium and the hypothalamus. Progesterone results in increased endometrial secretions and inhibits the release of GnRH in females. It also inhibits female reproductive behaviour as well as acting to maintain a pregnancy. Progesterone has no primary action in the male.

Testosterone (T)

The male sex hormone is called testosterone and this hormone is required for 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.

Regulation of Male Sex Hormones

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 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 in females and in sertoli cells 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 inhibits FSH secretion whilst in females it stimulates FSH secretion.

Activin

Activin is a glycoprotein that is produced within granulosa cells in females and sertoli cells in the male. The target tissue for activiin in the male is the epididymis whilst in the female it is the anterior pituitary gland, specifically gonadotroph cells. In males and females activin stimulates FSH secretion.

Prostaglandin F2α

Prostaglanin is a C₂O fatty acid and is produced within the uterine endometrium and vesicular glands. The target tissue in the female is the corpus luteum, uterine myometrium and ovulatory folicles. In the male foetus prostaglandin affects the the metabolic activity of spermatozoa and epididymal contractions. In the female prostaglandin results in luteolysis, the induction of tone and contractions within the uterus and ovulation.

Prostaglandin (PGE₂)

PGE₂ is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. It's target tissue in females is the corpus luteum and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum.

Human Chorionic Gonadotrophin (hCG)

hCG is a form of glycoprotein that is synthesised within the trophoblast cells of a blastocyst. In females the target tissue is the ovary where it results in the ovarian production of progesterone. In males hCG increases the growth of the foetal testes.

Equine Chorionic Gonadotrophin (eCG)

eCG is a form of glycoprotein that is produced from chorionic girdle cells. In females the primary target organ are the ovaries where they faciliate the formation of the accessory corpora lutea.

Placental Lactogen (PL)

Placental lactogen is a form of protein that is produced by the placenta. It's primary target tissue are the mammary glands where they stimulate milk production.