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.

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 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.

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.

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 granulosa cells, the placenta and the 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 follicular phase (proestrous and 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. More detailed information regarding corpus luteum formation and 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.

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.

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.

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 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.