Hormonal Aspects of the Female Reproductive System

Hello :) In this post I'll give an overview of the main functions of the ovary and describe the hormones and physiological events involved in the follicular and luteal phases of the oestrus cycle. We'll also take a look at the process of recruitment, selection, dominance and atresia in folliculogenesis and differentiate between the pre-antral and antral phases of folliculogenesis. I'll also explain the negative and positive feedback systems which are involved in regulating the female reproductive system and describe the physiological process and hormones involved in ovulation. We'll finish off by taking a look at the physiological effects of oestrogen and progesterone within the female body. Enjoy!

The Ovaries

The ovaries serve two important functions:

1. Oogenesis: this is the formation, development and release of female gametes (ova).
2. Steroid hormone synthesis: The ovaries produce steroidal hormones which orchestrate events associated with the oestrus cycle, pregnancy and parturition. 

The Oestrus Cycle

As explained in this post, the oestrus cycle can be divided into two major steps: the follicular phase and the luteal phase.  

The Follicular Phase:

This phase consists of four major physiological events:

1. Increased Luteinising Hormone (LH)/Follicle Stimulating Hormone (FSH) secretion from the anterior pituitary. The hypothalamus secretes GnRH which stimulates the anterior pituitary to secrete these hormones. The hypothalamus has a tonic centre, responsible for small regular GnRH pulses, and a surge centre, which is responsible for the preovulatory GnRH and LH surge.
2. Follicular growth and preparation for ovulation
3. Sexual receptivity due to the increased amount of oestrogen in the body
4. Ovulation

The main hormone produced by the developing follicles is oestrogen which immunologically prepares the reproductive tract for copulation, induces reproductive behaviour and controls the LH hormonal surge responsible for ovulation. Oestrogen also assists in folliculogenesis. 

Folliculogenesis refers to the growth and development of the primordial follicle within the ovary. It involves:

• Recruitment: a group of small follicles begin to grow and produce small amounts of oestradiol. At this stage progesterone is absent and this allows the concentration of GnRH and hence LH and FSH to increase. FSH causes follicular growth at the granulosa cells (we'll come back to these later on) while LH stimulates the synthesis of androstenedione by the Theca cells. This substance is converted to oestradiol in granulosa cells under the influence of FSH. Follicles must have FSH as well as oestradiol to develop. 
• Selection: Ninety per cent of follicles undergo atresia but those that don't are 'selected' to continue with growth and moderate oestradiol secretion. 
• Dominance: one or more follicles (this depends on the species) causes the other selected follicles to undergo atresia. The dominant follicles ovulate. This is because as the follicles increase in size, they produce more oestradiol. Oestradiol as well as inhibin produced by the granulosa cells work together to reduce the amounts of FSH and LH secreted. FSH is required by the follicles in order to develop, thus a decreased concentration of FSH induces atresia. The dominant follicles are able to survive because they have more FSH receptors than the other follicles and so can develop on smaller amounts of FSH.
• Atresia: This is the degeneration of follicles and may occur at any stage. 

Pre-Antral and Antral Phases

Developing follicles can be loosely categorised as either pre-antral or antral. The growth and differentiation of pre-antral follicles is controlled by locally produced growth factors and paracrine or autocrine messages. They do not require FSH or LH. Antral follicles experience a significant increase in follicle size and their growth is regulated by LH and FSH.

• Pre-Antral Phase: this includes:
• Primordial follicles: which are immature oocytes surrounded by a single layer of squamous follicle cells. 
• Primary follicles: this is when the squamous cells found in the primordial follicles become cuboidal granulosa cells. These follicles express FSH receptors but are gonadotropin independent. Granulosa cells are the female equivalent of sertoli cells (see this post). They secrete inhibin which suppresses FSH, synthesise and secret progesterone and convert androgens to oestrogens.
• Secondary follicles: In these cells, more than one layer of granulosa cells are present and the outer most layer is transformed into Theca. These follicles are also gonadotropin independent. 
• Antral Phase: which includes:
•  Graafian follicles: An antrum (fluid-filled cavity) develops in these follicles and they also have granulosa cells which have LH receptors. Graafian follicles are gonadotropin dependent and only the dominant follicles are selected.   

Ovulation

Oestrogen levels from the dominant follicle continue to increase and at the end of the follicular phase oestradiol levels reach a threshold. At threshold oestrogen has a positive feedback effect on the surge centre of the hypothalamus which causes the preovulatory LH surge from the anterior pituitary. This LH surge induces ovulation.

The preovulatory LH surge results in an increased blood flow to the dominant follicle and ovary which leads to oedema and increased follicular pressure. The surge also results in a rise in the prostaglandin F2α (PGF2α) which stimulates the contraction of ovarian smooth muscle leading to increased follicular pressure. PGF2α also causes the release of lysosomal enzymes which weakens the follicle wall. In addition, after the LH surge, the dominant follicle releases progesterone which causes the release of collagenases which also work to weaken the follicle wall. Increased follicular pressure and a weakened follicle wall leads to ovulation.

Summary of Feedback Effects

Oestrogen may play a negative feedback role as it suppresses LH and FSH at the level of the pituitary and hypothalamus. However, it is a weak inhibitor on its own and needs to be coupled with inhibin for maximum effect.

Oestrogen may also play a positive feedback role after it reaches threshold as it causes a surge of GnRH and LH which stimulates ovulation. However, the mechanism behind how it changes from negative feedback to positive feedback is unknown.

The Luteal Phase

The dominant hormone during this phase is progesterone. It consists of:

1. The formation of the corpus lutea (known as luteinisation).
2. Production of progesterone
3. Luteolysis: this is the irreversible degeneration of the CL and is characterised by decreased progesterone levels. It is necessary for the non-pregnant animal to resume folliculogenesis. The main factor here is PGF2α. What happens is oestrogen binds to its receptors on the endometrium and increases the formation of oxytocin receptors. Oxytocin, which is released from the posterior pituitary, binds to the receptors on the endometrium. This increases the secretion of PGF2α which interferes with the blood supply to the CL and inhibits its production of progesterone and this leads to luteolysis.
      

If no fertilisation occurs the corpus lutea (CL) will persist for about 14 days. During this time it secretes progesterone which inhibits GnRH and prevents more follicles from developing. After 14 days it undergoes luteolysis. If fertilisation does occur, the CL will persist and secrete progesterone in order to maintain pregnancy as it is the main source of progesterone.

Effects of Oestrogen and Progesterone on the Female Body

Oestrogen assists FSH in follicular growth; regulates the release of gonadotropins; prepares the external genitalia, vagina and uterus for copulation; enhances the transport of sperm to the oviduct; contributes to the growth and development of the mammary glands; increases myometrial tone; induces oestrus behaviour; and promotes other secondary sex characteristics. 

Progesterone is the 'hormone of pregnancy' as it creates favourable conditions for the development of the foetus. It has a negative feedback effect on GnRH, LH and FSH; stimulates the secretion of uterine endometrial glands create a good environment for the foetus; suppresses uterine myometrial contractions, counteracting the effects of oestrogen and oxytocin; and aids the growth and development of the mammary glands.



 That's all for this post, see you next time :)