Hormonal Control of the Ovarian Cycle

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The hypothalamus and pituitary gland regulate the ovarian cycle and ovulation. GnRH activates the anterior pituitary to produce LH and FSH, which stimulate the production of estrogen and progesterone by the ovaries.

Source: OpenStax Anatomy and Physiology

OpenStax Anatomy and Physiology

The process of development that we have just described, from primordial follicle to early tertiary follicle, takes approximately two months in humans. The final stages of development of a small cohort of tertiary follicles, ending with ovulation of a secondary oocyte, occur over a course of approximately 28 days. These changes are regulated by many of the same hormones that regulate the male reproductive system, including GnRH, LH, and FSH.

As in men, the hypothalamus produces GnRH, a hormone that signals the anterior pituitary gland to produce the gonadotropins FSH and LH. These gonadotropins leave the pituitary and travel through the bloodstream to the ovaries, where they bind to receptors on the granulosa and theca cells of the follicles. FSH stimulates the follicles to grow (hence its name of follicle-stimulating hormone), and the five or six tertiary follicles expand in diameter. The release of LH also stimulates the granulosa and theca cells of the follicles to produce the sex steroid hormone estradiol, a type of estrogen. This phase of the ovarian cycle, when the tertiary follicles are growing and secreting estrogen, is known as the follicular phase.

The more granulosa and theca cells a follicle has (that is, the larger and more developed it is), the more estrogen it will produce in response to LH stimulation. As a result of these large follicles producing large amounts of estrogen, systemic plasma estrogen concentrations increase. Following a classic negative feedback loop, the high concentrations of estrogen will stimulate the hypothalamus and pituitary to reduce the production of GnRH, LH, and FSH. Because the large tertiary follicles require FSH to grow and survive at this point, this decline in FSH caused by negative feedback leads most of them to die (atresia). Typically only one follicle, now called the dominant follicle, will survive this reduction in FSH, and this follicle will be the one that releases an oocyte. Scientists have studied many factors that lead to a particular follicle becoming dominant: size, the number of granulosa cells, and the number of FSH receptors on those granulosa cells all contribute to a follicle becoming the one surviving dominant follicle.

When only the one dominant follicle remains in the ovary, it again begins to secrete estrogen. It produces more estrogen than all of the developing follicles did together before the negative feedback occurred. It produces so much estrogen that the normal negative feedback doesn’t occur. Instead, these extremely high concentrations of systemic plasma estrogen trigger a regulatory switch in the anterior pituitary that responds by secreting large amounts of LH and FSH into the bloodstream. The positive feedback loop by which more estrogen triggers release of more LH and FSH only occurs at this point in the cycle.

It is this large burst of LH (called the LH surge) that leads to ovulation of the dominant follicle. The LH surge induces many changes in the dominant follicle, including stimulating the resumption of meiosis of the primary oocyte to a secondary oocyte. As noted earlier, the polar body that results from unequal cell division simply degrades. The LH surge also triggers proteases (enzymes that cleave proteins) to break down structural proteins in the ovary wall on the surface of the bulging dominant follicle. This degradation of the wall, combined with pressure from the large, fluid-filled antrum, results in the expulsion of the oocyte surrounded by granulosa cells into the peritoneal cavity. This release is ovulation.

Oocyte will travel towards the uterus, but there is one more important event that occurs in the ovarian cycle. The surge of LH also stimulates a change in the granulosa and theca cells that remain in the follicle after the oocyte has been ovulated. This change is called luteinization (recall that the full name of LH is luteinizing hormone), and it transforms the collapsed follicle into a new endocrine structure called the corpus luteum, a term meaning “yellowish body”. Instead of estrogen, the luteinized granulosa and theca cells of the corpus luteum begin to produce large amounts of the sex steroid hormone progesterone, a hormone that is critical for the establishment and maintenance of pregnancy. Progesterone triggers negative feedback at the hypothalamus and pituitary, which keeps GnRH, LH, and FSH secretions low, so no new dominant follicles develop at this time.

The post-ovulatory phase of progesterone secretion is known as the luteal phase of the ovarian cycle. If pregnancy does not occur within 10 to 12 days, the corpus luteum will stop secreting progesterone and degrade into the corpus albicans, a nonfunctional “whitish body” that will disintegrate in the ovary over a period of several months. During this time of reduced progesterone secretion, FSH and LH are once again stimulated, and the follicular phase begins again with a new cohort of early tertiary follicles beginning to grow and secrete estrogen.

Source:

Betts, J. G., Young, K. A., Wise, J. A., Johnson, E., Poe, B., Kruse, D. H., … DeSaix, P. (n.d.). Anatomy and Physiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/anatomy-and-physiology

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