Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized
and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development,
growth, pubertal maturation and reproductive processes of the body. FSH and luteinizing
hormone act synergistically in reproduction.
Structure FSH is a 35.5kD glycoprotein dimer. Its structure
is similar to those of LH, thyroid-stimulating hormone and, human chorionic gonadotropin.
The protein dimer contains 2 polypeptide units, labeled alpha and beta subunits. The alpha
subunits of LH, FSH, TSH and, hCG are identical and contain 92 amino acids. The beta subunits
vary. 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 sugar part of
the hormone is composed of fucose, galactose, mannose, galactosamine, glucosamine, and sialic
acid, the latter being critical for its biologic half-life. The half-life of FSH is 3–4 hours.
Genes The gene for the alpha subunit is located
on chromosome 6p21.1-23. It is expressed in different cell types. The gene for the FSH
beta subunit is located on chromosome 11p13, and is expressed in gonadotropes of the pituitary
cells, controlled by GnRH, inhibited by inhibin, and enhanced by activin.
Activity FSH regulates the development, growth, pubertal
maturation and reproductive processes of the human body.
In both males and females, FSH stimulates the maturation of germ cells.
In males, FSH induces Sertoli cells to secrete Androgen-binding proteins and its secretion
is being regulated by inhibin's negative feedback mechanism on Anterior Pituitary gland.
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 phase, there 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. Low frequency gonadotropin-releasing hormone pulses increase FSH mRNA levels in
the rat, however this doesn't directly correlate with an increase in circulating FSH. GnRH
has been shown to play an important role in the secretion of FSH, with hypothalamic-pituitary
disconnection leading to a cessation of FSH. GnRH administration leads to a return of FSH
secretion. FSH is subject to oestrogen feed-back from the gonads via the hypothalamic pituitary
gonadal axis.
Effects in females FSH stimulates the growth and recruitment
of immature ovarian follicles in the ovary. In early antral follicles, FSH is the major
survival factor that rescues the small antral follicles from apoptosis. In the luteal-follicle
phase transition period the serum levels of progesterone and estrogen decrease and no
longer suppress the release of FSH, consequently FSH peaks at about day three. The cohort of
small antral follicles is normally sufficiently in number to produce enough Inhibin B to lower
FSH serum levels. In addition, there is evidence that gonadotrophin
surge-attenuating factor produced by small follicles during the first half of the follicle
phase also exerts a negative feedback on pulsatile luteinizing hormone secretion amplitude, thus
allowing a more favorable environment for follicle growth and preventing premature luteinization.
(As a woman nears perimenopause, the number of small antral follicles recruited in each
cycle diminishes and consequently insufficient Inhibin B is produced to fully lower FSH and
the serum level of FSH begins to rise. Eventually the FSH level becomes so high that downregulation
of FSH receptors occurs and by menopause any remaining small secondary follicles no longer
have FSH receptors.) When the follicle matures and reaches 8–10 mm
in diameter it starts to secrete significant amounts of estradiol. Normally in humans only
one follicle becomes dominant and survives to grow to 18–30 mm in size and ovulate,
the remaining follicles in the cohort undergo atresia. The sharp increase in estradiol production
by the dominant follicle 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.
The decrease in serum FSH level causes the smaller follicles in the current cohort to
undergo atresia as they lack sufficient sensitivity to FSH to survive. Occasionally two follicles
reach the 10 mm stage at the same time by chance and as both 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. Effects in males
FSH stimulates primary spermatocytes to undergo the first division of meiosis, to form secondary
spermatocytes. FSH enhances the production of androgen-binding
protein by the Sertoli cells of the testes by binding to FSH receptors on their basolateral
membranes, and is critical for the initiation of spermatogenesis.
Measurement Follicle stimulating hormone is typically
measured in the early follicular phase of the menstrual cycle, typically day three to
five, counted from last menstruation. At this time, the 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 is measured in International Units. For Human Urinary FSH, one IU is defined as the
amount of FSH that has an activity corresponding to 0.11388 mg of pure Human Urinary FSH.
For recombinant FSH, one IU corresponds to approximately 0.065 to 0.075 µg of a "fill-by-mass"
product. Disease states
FSH levels are normally low during childhood and, in females, high after menopause.
High FSH levels The most common reason for high serum FSH
concentration is in a female who is undergoing or has recently undergone menopause. High
levels of Follicle-Stimulating Hormone indicate that the normal restricting feedback from
the gonad is absent, leading to an unrestricted pituitary FSH production.
If high FSH levels occur during the reproductive years, it is abnormal. Conditions with high
FSH levels include: Premature menopause also known as Premature
Ovarian Failure Poor ovarian reserve also known as Premature
Ovarian Aging Gonadal dysgenesis, Turner syndrome
Castration Swyer syndrome
Certain forms of CAH Testicular failure.
Klinefelter syndrome Most of these conditions are associated with
subfertility and/or infertility. Therefore high FSH levels are an indication of subfertility
and/or infertility. Low FSH levels
Diminished secretion of FSH can result in failure of gonadal function. This condition
is typically manifested in males as failure in production of normal numbers of sperm.
In females, cessation of reproductive cycles is commonly observed. Conditions with very
low FSH secretions are: Polycystic Ovarian Syndrome
Polycystic Ovarian Syndrome + Obesity + Hirsutism + Infertility
Kallmann syndrome Hypothalamic suppression
Hypopituitarism Hyperprolactinemia
Gonadotropin deficiency Gonadal suppression therapy
GnRH antagonist GnRH agonist.
Use as therapy
FSH is used commonly in infertility therapy, mainly for ovarian hyperstimulation as part
of IVF. In some cases, it is used for reversal of anovulation as well.
FSH is available mixed with LH activity in various menotropins including more purified
forms of urinary gonadotropins such as Menopur, as well as without LH activity as recombinant
FSH. Potential role in vascularization of solid
tumors Elevated FSH receptor levels have been detected
in the endothelia of tumor vasculature in a very wide range of solid tumors. FSH binding
is thought to upregulate neovascularization via at least two mechanisms – one in the
VEGF pathway, and the other VEGF independent – related to the development of umbilical vasculature
when physiological. This presents possible use of FSH and FSH-receptor antagonists as
an anti tumor angiogenesis therapy. References
External links FSH - Lab Tests Online