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Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is subject to oestrogen feed-back from the gonads via the hypothalamic pituitary gonadal axis. . Hypothalamic Control of Pituitary FSH- Regulatory Proteins and Their Relationship to Changes in FSH Synthesis and Secretion". Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are called of testosterone, which is converted into estrogen by adjacent granulosa cells. FSH. LH. Female. stimulates ovary to produce steroids. ovary will produce estradiol during follicular phase and progesterone during luteal phase. surge at.
The discharge of the gonadotropins, FSH and LH, induces the production of estradiol and progesterone from the ovary which, in turn, through a feedback mechanism, influence the pattern of release of GnRH from the hypothalamus. GnRH is released in a pulsatile fashion and it is the frequency and amplitude of these pulses, in addition to the sensitivity of the pituitary gonadotrophs, that dictate the pattern of the release of the two gonadotropins.
The GnRH pacemaker is principally influenced by the ovarian steroids but many other factors, including opiates, catecholamines, neuropeptide Y, etc. If GnRH is released in a constant, non-pulsatile fashion, gonadotropin release is suppressed due to an apparent desensitization of the pituitary GnRH receptors. Pulsatile release of GnRH and fluctuations in the pattern of this pulsatility are thus integral features in the normal functioning of the ovulatory cycle.
As GnRH cannot be detected in human peripheral circulation, we have relied on the correlation with LH pulsatile release for our information on variations of pulsatility through the ovulatory cycle and in pathological conditions. Pulses of FSH are much more difficult to detect due to its longer half-life. In the follicular phase of a normal cycle, pulses of LH reflecting GnRH can be detected every 60—90 minutes.
Dramatic changes occur immediately preceding the pre-ovulatory LH surge. Hypothetically, the LH surge could be generated by an enormous discharge of GnRH or a temporary release from inhibition of pituitary LH discharge and a consequent increased pituitary sensitivity. Practically, both mechanisms are probably involved in creating the central event of the ovulatory cycle.
Speculation is rife surrounding the existence of a proposed gonadotropin surge attenuating factor, produced by granulosa cells, which inhibits pituitary LH discharge.
Although its structure is not yet known, a substance with this property has been isolated. Following ovulation, under the influence of rising progesterone concentrations, the frequency of the LH pulses gradually decreases from one every 2—4 hours in the early luteal phase to every 8—12 hours towards the end of the cycle. The amplitude of LH pulses in the luteal phase is significantly greater than in the follicular phase. The fluctuations in the frequency and amplitude of GnRH pulsatile release are central in dictating the pattern of release of FSH and LH and, in turn, the triggering of the ovulatory process and ovarian steroid production.
This knowledge of the basic physiology of the pattern of release and action of GnRH has brought with it many clinical implications. Induction of ovulation for women who have hypothalamic hypogonadrophic hypogonadism is very successful when GnRH is administered in a pulsatile fashion with one pulse every 60—90 minutes. This is an ideal example of pure substitution therapy.
The search for an agonist to boost GnRH action proved to have exactly the opposite eventual effect due to desensitization of GnRH receptors. These compounds are now very widely used before and during ovarian hyperstimulation for IVF to prevent premature LH surges.
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The use of GnRH antagonists is now also routine for use during controlled ovarian stimulation for IVF as they do not induce an initial, fleeting gonadotropin release as do the agonists, but an immediate decrease in their concentrations. Follicle stimulating hormone FSH The amount and timing of FSH release by the anterior pituitary changes throughout the ovulatory cycle.
This mechanism is influenced by many factors. With the sudden demise of the corpus luteum which immediately precedes menstruation, the negative feedback effects of estradiol, progesterone and inhibin A on FSH secretion are suddenly lost so that FSH is secreted in relatively large quantities during menstruation itself. This rise in FSH concentrations stimulates the growth of antral follicles, granulosa cell proliferation and differentiation.
It also encourages the action of the enzyme aromatase in the conversion of the basic androgens, androstendione and testosterone to estrogens. The sum total of these actions results in increasing estradiol and inhibin B concentrations, feedback mechanisms come into play and there is a consequent reduction of FSH concentrations. At mid-cycle, in tandem with the LH surge, there is a temporary increase in FSH secretion, more like a blip, whose significance is not clear.
It may be a mere byproduct of the GnRH surge or may have a function in preparing a cohort of small antral follicles for the next cycle. With the formation of the corpus luteum and the outpouring of both estradiol and progesterone, the negative feedback mechanism comes into play and continues its suppression of FSH release until just before the next menstruation. The main undulations in FSH levels throughout the ovulatory cycle are very simply illustrated in Fig.
Hormonal, follicular and endometrial changes across the phases of the ovulatory cycle. FSH is a hormone of many roles. It is a promotor of: Granulosa cell proliferation and differentiation 2.
Antral follicle development 4. Induction of LH receptors on the dominant follicle 5. Inhibin synthesis In addition to these functions, the decrease in FSH concentrations with rising estrogen concentrations is thought to play an important part in the selection of the dominant follicle.
The declining secretion of FSH prevents multiple follicular development, as only the largest of the developing follicles stays above the FSH threshold, has the most FSH receptors, remains most sensitive to FSH and produces most estrogen. It is then less sensitive to the declining FSH concentrations and can continue to develop while others fade into atresia due to lack of enough FSH stimulation.
The induction of LH receptors on the largest developing follicle s enables LH to take a part in the development of the dominant follicle in the late follicular phase and prepare it for the oncoming LH surge.
This basic knowledge of the mode of action of FSH, particularly regarding the FSH threshold for follicular growth, has influenced a change in ovulation induction regimes.
This has become particularly important in the development of a chronic low-dose regimen for the induction of mono-follicular ovulation and the avoidance of multiple pregnancies and ovarian hyperstimulation syndrome.
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Luteinizing hormone LH During the early and mid-follicular phase, the secretion of LH is relatively quiet with pulses every 60—90 minutes and a fairly constant low concentration of circulating LH.
However, this is the calm before the storm. An enormous climax is reached with the onset of the LH surge in the late follicular phase, the central event of the ovulatory cycle Fig. Concentrations of LH rise to 10—20 times their resting level during the rest of the cycle. The duration of the surge is 36—48 hours.
The LH surge, without which ovulation does not occur, is brought about by a combination of circumstances. Principally, there is a dramatic switch from a negative to a positive feedback action of estradiol at both the pituitary and hypothalamic level, triggered when persistently increasing estradiol concentrations reach a critical point.
LH secreting pituitary gonadotrophs clearly become highly sensitive to GnRH stimulation, probably by increasing their numbers of GnRH receptors, a GnRH surge occurs and a small rise in progesterone levels in the late follicular phase may also have a triggering role.
The pre-ovulatory LH surge has a number of key functions: Triggering of ovulation and follicular rupture about 36 hours after the surge. Disruption of the cumulus—oocyte complex. Induction of the resumption of oocyte meiotic maturation. Luteinization of granulosa cells.
Following the formation of the corpus luteum, increasing concentrations of progesterone slow down the frequency of the LH GnRH pulses to one every 3 then one every 4 hours. Concentrations of LH once again dip down to baseline levels. It is therefore, not clear what kind of influence LH levels have on the maintenance of the corpus luteum.
The luteal phase is thus the constant part of the ovulatory cycle whereas the follicular phase is much more likely to be prone to changes in duration. Two cells — two gonadotropins Outside the tumultuous events of the mid-cycle surge, the main function of LH is to encourage the production of androgens by theca cells.
Here they meet aromatase CYP19whose function it is to convert them into estrogens, mainly estradiol but also estrone. Aromatase action, and therefore estrogen production, is controlled by FSH. The two-cell, two gonadotropin hypothesis. In clinical practice, hCG has been used as an excellent substitute for the LH surge in the triggering of ovulation as it binds to the LH receptor. It has a much longer half-life than LH.
The current availability of pure, recombinant LH and recombinant FSH have enabled the further investigation of the physiology of the ovulatory cycle. High doses of recombinant LH are capable of triggering ovulation.
The availability of these preparations as separate entities has prompted a large number of experiments to examine what is their exact function and necessity throughout the cycle. Estradiol Estrogens are the basic female hormones and estradiol is the most important as far as the ovulatory cycle is concerned.
Follicle-stimulating hormone - Wikipedia
The synthesis of estradiol by granulosa cells is a function of the action of FSH. FSH stimulates the enzyme aromatase CYP19 to convert the substrate of basic androgens, androstendione and testosterone, to estradiol in granulosa cells.
The production of this vital hormone thus requires the availability of the androgen substrate, whose production in theca cells is promoted by LH, and then the action of FSH. The key functions of estradiol in the ovulatory cycle are: As a cog in a negative feedback mechanism suppressing the secretion of FSH and so aiding in the selection of the dominant follicle and preventing multifollicular development in the mid-late follicular phase.
Triggering of the LH surge in mid-cycle by initiating a positive feedback mechanism when its concentrations rise to a critical level. Estradiol concentrations are at their lowest during menstruation.
The FSH induced follicular development brings about rapidly rising estradiol production in the mid-follicular phase. When estradiol levels attain a persistently high critical concentration in the late follicular phase, they induce the LH surge.
Following ovulation, estradiol concentrations dip temporarily but are revived by corpus luteum activity. With the demise of the corpus luteum, estradiol concentrations sink rapidly to their lowest levels and invoke the FSH rise immediately preceding menstruation Fig. Please help improve it to make it understandable to non-expertswithout removing the technical details. February Learn how and when to remove this template message FSH is a Genes[ edit ] In humans, the gene for the alpha subunit is located at cytogenetic location 6q The gene for the FSH beta subunit is located on chromosome 11p13, and is expressed in gonadotropes of the pituitary cells, controlled by GnRHinhibited by inhibinand enhanced by activin.
FSH regulates the development, growth, pubertal maturation and reproductive processes of the human body. In both males and females, FSH stimulates the maturation of primordial germ cells.
In males, FSH induces Sertoli cells to secrete androgen-binding proteins ABPsregulated by inhibin 's negative feedback mechanism on the anterior pituitary. Specifically, activation of Sertoli cells by FSH sustains spermatogenesis and stimulates inhibin B secretion. In females, FSH initiates follicular growth, specifically affecting granulosa cells.
With the concomitant rise in inhibin B, FSH levels then decline in the late follicular phase. This seems to be critical in selecting only the most advanced follicle to proceed to ovulation. At the end of the luteal phasethere is a slight rise in FSH that seems to be of importance to start the next ovulatory cycle. Control of FSH release from the pituitary gland is unknown.
FSH is subject to oestrogen feed-back from the gonads via the hypothalamic pituitary gonadal axis. Reference ranges for the blood content of follicle-stimulating hormone levels during the menstrual cycle. Effects in females[ edit ] FSH stimulates the growth and recruitment of immature ovarian follicles in the ovary. In the luteal-follicle phase transition period the serum levels of progesterone and estrogen primarily estradiol decrease and no longer suppress the release of FSH, consequently FSH peaks at about day three day one is the first day of menstrual flow.
The cohort of small antral follicles is normally sufficient in number to produce enough Inhibin B to lower FSH serum levels. In addition, there is evidence that gonadotropin surge-attenuating factor produced by small follicles during the first half of the follicle phase also exerts a negative feedback on pulsatile luteinizing hormone LH secretion amplitude, thus allowing a more favorable environment for follicle growth and preventing premature luteinization.
The sharp increase in estradiol production by the dominant follicle possibly along with a decrease in gonadotrophin surge-attenuating factor cause a positive effect on the hypothalamus and pituitary and rapid GnRH pulses occur and an LH surge results. The increase in serum estradiol levels cause a decrease in FSH production by inhibiting GnRH production in the hypothalamus.