Produced by the pituitary, partially in response to gonadotropin-releasing hormone and partially in response to pituitary activin.
FSH is under inhibitory control by estradiol and the inhibiting peptides A and B…
Inhibin B is the principal regulator of FSH in the follicular phase of the cycle.
Inhibin B is a product primarily of the corpus luteum and placenta and largely contributes to FSH suppression during pregnancy.
FSH is an indirect measure of follicular reserve that requires an intact hypothalamus-pituitary axis.
FSH fluctuates almost 10 times over the course of a normal menstrual cycle.
FSH levels determined within the first five days of onset of menstrual bleeding are commonly used to project ovarian response to fertility treatments.
FSH levels are typically measured within five days of the onset of menses, when is most consistent and its highest.
Follicle-stimulating hormone
Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone.
It is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland.
FSH is typically measured in the early follicular phase of the menstrual cycle, typically day three to five, counted from last menstruation.
In the early follicular phase, levels of estradiol and progesterone are at the lowest point of the menstrual cycle.
FSH levels in this time is often called basal FSH levels, to distinguish from the increased levels when approaching ovulation.
FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body.
It works with luteinizing hormone (LH) in the reproductive system.
It consists of two polypeptide units, alpha and beta.
Its structure is similar to those of luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and human chorionic gonadotropin (hCG).
The alpha subunits of the glycoproteins LH, FSH, TSH, and hCG are identical, and consist of 96 amino acids.
The beta subunits vary.
Both alpha and beta subunits are required for biological activity.
FSH has a beta subunit of 111 amino acids which confers its specific biologic action, and is responsible for interaction with the FSH receptor.
The gene for the alpha subunit is located at cytogenetic location 6q14.3.
The gene is expressed in two cell types, most notably the basophils of the anterior pituitary.
The gene for the FSH beta subunit is located on chromosome 11p13.
The gene for the FSH beta subunit is expressed in gonadotropes of the pituitary cells, controlled by GnRH, inhibited by inhibin, and enhanced by activin.
It regulates the development, growth, pubertal maturation and reproductive processes of the human body.
FSH stimulates the maturation of primordial germ cells in both males and females.
In males, FSH induces Sertoli cells to secrete androgen-binding proteins.
FSH is regulated by inhibin’s negative feedback mechanism on the anterior pituitary.
Activation of Sertoli cells by FSH sustains spermatogenesis and stimulates inhibin B secretion.
In females, FSH initiates follicular growth, and specifically affects granulosa cells.
With a rise in inhibin B, FSH levels decline in the late follicular phase, and only the most advanced follicle to proceeds to ovulation.
GnRH has been shown to play an important role in the secretion of FSH.
GnRH administration leads to a return of FSH secretion.
FSH is subject to estrogen feed-back from the gonads via the hypothalamic pituitary gonadal axis.
FSH stimulates the growth and recruitment of immature ovarian follicles.
FSH is the major survival factor that rescues the small ovarian antral follicles from apoptosis.
In the luteal-follicle phase the serum levels of progesterone and estrogen decrease and no longer suppress the release of FSH.
FSH peaks at about day three of the menstrual cycle.
The small antral follicles is normally sufficient in number to produce enough Inhibin B to lower FSH serum levels.
Gonadotropin surge produced by small follicles during the first half of the follicle phase has negative feedback on pulsatile luteinizing hormone (LH) secretion amplitude.
As perimenopause occurs the number of small antral follicles recruited in each cycle diminishes.
As the number of small astral ovarian follicles diminish, insufficient Inhibin B is produced to lower FSH and the serum level of FSH begins to rise.
Eventually downregulation of FSH receptors occurs and by postmenopause any remaining small secondary follicles no longer have FSH nor LH receptors.
When an ovarian follicle matures and reaches 8–10 mm in diameter it secretes significant amounts of estradiol.
Usually only one follicle becomes dominant and survives to grow to 18–30 mm in size and ovulate, while the remaining follicles in the cohort undergo atresia.
The dominant follicle sharply increases estradiol production by the dominant follicle and causes 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.
Subsequently, the decrease in serum FSH level causes the smaller follicles to undergo atresia as they lack sufficient sensitivity to FSH to survive.
Occasionally when follicles reach the 10 mm stage at the same time, and are equally sensitive to FSH both survive and grow in the low FSH environment and thus two ovulations can occur in one cycle possibly leading to non-identical twins.
In males FSH stimulates primary spermatocytes to undergo the first division of meiosis, to form secondary spermatocytes.
FSH enhances androgen-binding protein production by the Sertoli cells of the testes by binding to FSH receptors on their basolateral membranes,
FSH is critical for the initiation of spermatogenesis.
FSH is measured in International Units (IU).
One IU is defined as the amount of FSH that has an activity corresponding to 0.11388 mg of pure Human Urinary FSH.
FSH levels are normally low during childhood and, in females, high after menopause.
The most common reason for high serum FSH concentration is in a female who is undergoing or has recently undergone menopause.
Elevated levels of FSH indicate the normal feedback from the gonad is absent, leading to an unrestricted pituitary FSH production.
FSH may contribute to postmenopausal osteoporosis and cardiovascular disease.
High FSH levels during the reproductive years is abnormal.
Conditions with high FSH levels include:
Premature menopause
Poor ovarian reserve
Gonadal dysgenesis
Turner syndrome
Castration
Testicular failure
Klinefelter syndrome
Systemic Lupus Erythematosus
Most conditions with high FSH levels are associated with subfertility and/or infertility.
Low FSH levels are associated with:
Failure of gonadal function, hypogonadism, typically manifested in males as failure in production of normal numbers of sperm.
In females, cessation of reproductive cycles is commonly observed.
Conditions associated with very low FSH secretions:
Polycystic Ovarian Syndrome
Kallmann syndrome
Hypothalamic suppression
Hypopituitarism
Hyperprolactinemia
Gonadotropin deficiency
Gonadal suppression therapy
GnRH antagonist
GnRH agonist
FSH is used commonly in infertility therapy, mainly for ovarian hyperstimulation as part of IVF.
It can be used in ovulation induction for reversal of anovulation as well.
FSH is available mixed with LH activity.
Elevated FSH receptor levels have been detected in the endothelia of tumor vasculature in a very wide range of solid tumors.