Regulation Of The Menstrual Cycle

Autocrine And Paracrine Growth Factors

These variables exhibit expression in the anterior pituitary and both ovaries. Activin and inhibin are the two primary growth factors discussed in this article. They are both members of the TGF family of polypeptides.

The mullerian hormone is another element that is a member of the same family. These growth factors consist of two subunits, α and Ϻ, which are linked by a disulfide bond. Since there is only one type of α subunit, the type of inhibin is determined by the type of Ϻ\ subunit.

The beta A subunit is present in Inhibin A, while the beta B subunit is present in Inhibin B. Inhibins A and B both serve the same purpose. Corpus Luteum produces Inhibin A. Inhibin B is produced by the ovarian follicle's granulosa. Inhibin thus primarily originates from the ovary. The anterior pituitary is the primary source of folistatin and activin.

There are two ẞ subunits in activin. Follistatin is a glycopeptide with a different structure.

Function Of Inhibin And Activin

As its name implies, inhibitin works endocrinely to prevent the anterior pituitary gland from producing the hormone FSH.

It is crucial to remember that activin, folistatin, and inhibitin all affect the hormone FSH.

Conversely, activin functions through both autocrine and paracrine processes. It is released from the ovarian follicle and acts as an autocrine to stimulate the release of growth hormone (FSH) from the ovaries. It is secreted from the anterior pituitary and acts as an autocrine to stimulate the pituitary's release of FSH. Follicstatin suppresses the anterior pituitary's ability to produce FSH by binding to activin.

Also Read: Surgical Anatomy Of Anterior Abdominal Wall

Functional Synchronization Of Activin And Inhibin

Androgens are generated in the theca cell before being transferred to the granulosa cell. FSH stimulation has aromatized them there. Inhibin B suppresses the anterior pituitary gland's ability to produce FSH. FSH also encourages the granulosa cells to make activin and Inhibin B.

It's crucial to remember that estrogen plays a major role in the establishment of a healthy follicle, whereas androgen is also necessary. However, too much androgen also stunts follicle growth, which is bad for development. Activin suppresses the production of androgens while simultaneously stimulating the activity of aromatase.

Feedback Control Of HPO AXIS

The pituitary produces a positive feedback signal when there is a hormonal deficit, such as in menopausal women. Consequently, the levels of LH and FSH rise. An excess of ovarian hormones provides the pituitary with negative feedback.

The menstrual cycle acts as a switch to toggle between these feedback routes, one positive and one negative. During the early follicular phase of the menstrual cycle, the level of estrogen increases. The anterior pituitary receives a negative input from this elevated level, and the GnRH neurons also receive a negative signal from it.

The pulsatile secretion from GnRH neurons is inhibited by estrogen through the inhibition of kisspeptin release. As the estrogen cycle progresses and surpasses the threshold, it provides positive input to the higher centers during the cycle.

More FSH and LH are secreted from the pituitary and pulsatile GnRH is released from the hypothalamus as a result of this positive feedback, which is activated on both anterior pituitary and GnRH neurons.

Progesterone is the other hormone that regulates this axis. The anterior pituitary receives positive input when progesterone levels are lower. When progesterone levels rise during the luteal phase, the hypothalamus is inhibited in response.

In the end, this results in less FSH and LH output.  As a result, progesterone supplements included in contraceptive pills prevent ovulation. This inhibition only occurs at the hypothalamus level since it is achieved by reducing the production of LH rather than FSH.

Regulation Of Menstrual Cycle

 All of the hormone levels are low on day 28 of the cycle. The pulsatile GnRH secretion is modest at this stage due to the high progesterone level. The pulsatile secretion will gradually change in order to raise the level of FSH. Initially, the development of the follicles is aided by an increase in the FSH level.

The higher FSH level will now activate the follicles that have grown through the gonadotropin independent period, which lasted for roughly 70 days. As a result, only the dominant follicle will be kept for continued development. For this reason, a number of follicles in the preantral or antral phases will be chosen at first. Therefore, the follicle that fits the best will be chosen at this time for maturity.

Estradiol levels rise at first, but gradually; The developing follicles produce estrogen.  As previously mentioned, the granulosa cells in the follicle secrete Inhibin B, which prevents the hormones from the upper HPO axis from being secreted.

Consequently, the FSH level falls. More FSH also encourages the formation of LH receptors in the granulosa cells. Only the dominant follicle secretes the largest quantity of FSH during this phase because it has developed the maximum number of FSH receptors.

Also Read: Ovary  Structure And Stage Of Differentiation

Selection Of Dominant Follicle

As previously indicated, FSH causes the granulosa cells to express more FSH and LH receptors, which helps to choose the dominant follicle. Atrophied follicles will experience atrophy.

Meiosis is inhibited by the antral and preantral follicles' released AMH. The dominant follicle has been chosen between days five and seven. The dominant follicle is the one with the greatest number of FSH receptors, the highest activity of aromatase, and it keeps growing. It keeps secreting estrogen, which causes an increase in estrogen.

The dominant follicle should produce an estradiol spike that lasts for at least four hours and reaches a threshold level of at least 200 pg/ml. Only then does a successful ovulation occur, and the LH surge starts. It is anticipated that ovulation will occur 10–12 hours following the peak of LH and 24–36 hours following the peak of Estradiol.

Therefore, ovulation does not occur and results in anovulation if the surge of estrogen does not reach the threshold level. The start of the LH surge is the most crucial sign to determine when ovulation is likely to occur. Therefore, a successful ovulation takes place 36 hours after the start of the LH surge.

The release of progesterone is minimal during the late follicular phase. After that, progesterone starts to increase. As previously mentioned, FSH also causes the granulosa cells to produce LH receptors, which in turn causes the secretion of progesterone.

The pituitary and hypothalamus receive a favorable reaction from this modest amount of progesterone, which aids in sustaining the LH surge. The midcycle increase in progesterone causes the FSH surge. The dominant follicle is ultimately stimulated by this FSH surge to develop into a healthy corpus luteum.

The spike in LH and FSH levels decreases after ovulation. The corpus luteum secretes more progesterone now, and it also secretes inhibin A, which inhibits FSH and causes a negative feedback loop in the hypothalamic GnRH nucleus.

There is no more inhibition and a positive feedback loop to the anterior pituitary and the hypothalamus, which results in the increased secretion of FSH needed for the follicular growth of the new cycle. In the luteal phase, the corpus luteum also secretes more estradiol. After the corpus luteum dies, the progesterone level and Inhibin A level go down.

Also Read: Mechanism Of Sex Steroid Hormones 

Normal Menstrual Cycle Characteristics

The terminology is displayed in the above table in accordance with the FIGO 2020 rules.  The cycle lasts between 28 and 38 days on average.  The flow lasts somewhere between four and eight days.

In a cycle, blood flow between 5 and 80 milliliters is regarded as typical.  Regularity, or the variance from cycle to cycle, can range from two to twenty days.  A cycle is considered frequent if it lasts for fewer than twenty-four days.

A cycle is considered to be uncommon if it lasts longer than 38 days. A lengthy duration of flow is one that lasts longer than eight days. A flow that lasts fewer than 4.5 days is referred to as a truncated flow. Heavy bleeding occurs when a cycle's blood flow exceeds 80 milliliters, while scanty bleeding occurs when it is less than 5 milliliters.

It is crucial to remember that women's perceptions play a significant role in determining blood flow levels. A cycle is considered irregular if its deviation lasts longer than 20 days.

Also Read: Neuroendocrinology Of Female Reproduction And Steroid Hormones

Anovulatory Cycles

There are several patterns associated with chronic anovulatory cycles, including amenorrhea and infrequent periods that may be followed by heavy menstrual bleeding (HMB).

In addition, irregular cycles may exist with or without HMB. The anovulatory cycle is characterized by what is essentially an estrogen withdrawal hemorrhage. In this case, numerous follicles grow together during the follicular phase, and one follicle becomes dominant, but ultimately no ovulation occurs.
As a result, neither the corpus luteum nor the progesterone level develop. During this anovulatory cycle, estrogen stimulates the formation of the uterine lining.

This is an estrogen withdrawal hemorrhage, a feature of the anovulatory cycle, when the endometrium outgrows its blood supply and eventually sheds off as it continues to proliferate. The follicles will also die at the same time.  As a result, estrogen levels also decrease, which is why estrogen withdrawal bleeding occurs.Most of the time, this kind of bleeding is likely to be severe.

The timing of this kind of bleeding is often irregular since the time of the estrogen withdrawal is not clearly defined.
Anovulatory cycle may be the cause of a woman's irregular period and severe bleeding.  Conversely, if a woman is experiencing a regular period, she probably has an ovulatory cycle, while there's a slim chance it could also be anovulatory.

Also Read: Puerperium: Understanding the Postpartum Period

Questions

Q. Name a growth factor that works both in autocrine and paracrine manner.?

Activin functions both in autocrine and paracrine manner.

Q. What is the function of Inhibin?

Inhibin inhibits the secretion of FSH from the anterior pituitary.

Q. When does the ovulation occur?

The ovulation occurs in the mid cycle after about 10-12 hours after the LH surge and 24-36 hours after the Estrogen surge.

Also Read: From HPO Axis To Ovulation

Hope you found this blog helpful for your Basic Sciences OBS-GYN preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.