Follicle-stimulating hormone

Follicle-stimulating hormone (FSH) is a hormone synthesised and secreted by gonadotropes in the anterior pituitary gland. FSH and LH act synergistically in reproduction:

• In women, in the ovary FSH stimulates the growth of immature Graafian follicles to maturation. As the follicle grows, it releases inhibin, which shuts off the FSH production.
• In men, FSH enhances the production of androgen-binding protein by the Sertoli cells of the testes, and is critical for spermatogenesis.

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Structure

FSH is a glycoprotein. Each monomeric unit is a protein molecule with a sugar attached to it; two of these make the full, functional protein. Its structure is similar to those of LH, TSH, and hCG. 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 118 amino acids (FSHB), 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, pubertol maturation, and reproductive processes of the human body. In both males and females, FSH stimulates the maturation of germ cells. 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.

Like its partner, LH, FSH release at the pituitary gland is controlled by pulses of gonadotropin-releasing hormone (GnRH). Those pulses, in turn, are subject to the oestrogen feed-back from the gonads.

Disease states

FSH levels are normally low during childhood and, in women, high after menopause.

High FSH levels

High levels of Follicle-Stimulating Hormone are indicative of situations where the normal restricting feedback from the gonad is absent, leading to an unrestricted pituitary FSH production. Whereas this is normal in women leading up to and during postmenopause, it is abnormal during the reproductive years.

If the FSH level is high during the reproductive years, this may be a sign of:

1. Premature menopause also known as Premature Ovarian Failure
2. Gonadal dysgenesis, Turner syndrome
3. Castration
4. Swyer syndrome
5. Certain forms of CAH
6. Testicular failure.

Low FSH levels

Diminished secretion of FSH can result in failure of gonadal function (hypogonadism). This condition is typically manifest 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:

1. Kallmann syndrome
2. Hypothalamic suppression
3. Hypopituitarism
4. Hyperprolactinemia
5. Gonadotropin deficiency
6. Gonadal suppression therapy
   1. GnRH antagonist
   2. GnRH agonist (downregulation).

Availability

FSH is available mixed with LH in the form of Pergonal or Menopur, and other more purified forms of urinary gonadotropins, as well as in a pure forms as recombinant FSH (Gonal F, Follistim). It is used commonly in infertility therapy to stimulate follicular development, notably in IVF therapy, as well as with interuterine insemination (IUI).