Clinical Significance

Human follicle stimulating hormone (hFSH, follitropin) is made up of two non-identical, covalently-associated glycoprotein subunits, denoted alpha and beta. It has been reported that the beta subunit of the 30,000 dalton molecular weight hFSH contains two asparagine-linked carbohydrate chains. The alpha subunit is similar in structure for the glycoproteins hFSH, hCG, hLH, and hTSH. It is differences in the beta subunit of these glycoproteins which contributes to immunological and physiological specificity.

In the female, hFSH stimulates follicular growth and, in conjunction with hLH, stimulates estrogen seccretion and ovulation. Following ovulation, hFSH and hLH are believed to be responsible for the transformation of the ruptured follicle into a corpus luteum and to influence the secretion of progesterone by the luteal cells.

hFSH is secreted by the gonadotropic cells of ther anterior lobe of the pituitary gland in response to gonadotropin releasing hormone (GnRH) from the medial basal hypothalamus. Both hFSH and hLH are secreted in a pulsatile nature, however, this is less noticeable for hFSH perhaps due to the longer half life of hFSH in circulation. Levels of circulating hFSH vary in response to estradiol and progesterone. In a normal menstrual cycle, a slight peak of hFSH is observed toward the end of the luteal phase (most likely triggered by a fall in estradiol and progesterone which eliminates the negative feedback effect.) This begins the growth and maturation of ovarian follicles. The levels of hFSH then fall and remain low through the follicular phase (due to negative feedback from estradiol and progesterone produced by the developing follicle.) At mid-cycle GnRH triggers a rise in hFSH.

The function of this mid-cycle peak of hFSH is unknown. Following this rise, hFSH is suppressed during the luteal phase by negative feedback from estradiol. Near the end of the menstrual cycle the small hFSH rise then begins the follicular maturation of the next cycle. Variation in cycle lengths observed in the normally menstruating female are due to variations in the length of the follicular phase. In the menopausal female, hFSH levels are elevated in response to decreased production of ovarian estrogens and progesterones which eliminates the negative feedback mechanism on the pituitary gland. As a result, ovulation and menstrual cycles decrease and eventually cease.

In the male, hFSH stimulates spermatogenesis through receptors on the Sertoli cells which are present in the seminigerous tubules of the tests. While both hLH and hFSH are required for normal maturation of spermatozoa, hFSH is less sensitive to feedback inhibition by testosterone. hFSH is thought to be regulated in part by the peptide inhibin which is produced by the Sertoli cells in males and granulosa in females.

hLH and hFSH levels are commonly determined in investigations of menstrual, fertility, and pubertal developmental disorders such as premature ovarian failure, menopause, ovulatory disorders, and pituitary failure. The ratio of hLH/hFSH has been used to assist in the diagnosis of polycystic ovary disease. Low levels of hLH and hFSH may indicate pituitary failure while elevated hLH and hFSH levels along with decreased levels of gonadal steroids may indicate gonadal failure (menopause, ovariectomy, premature ovarian syndrome, Turner's syndrome). Low gonadotropin levels are usually oberved in females taking oral steroid-based contraceptives. In the male, elevated hFSH and hLH eith low levels of gonadal steroids may indicate testicular failure or anorchia. In Klinefelter's syndrome hFSH may be elevated due to Sertoli cell failure.

_{Source: Access FSH IFU #33520, 12/5/16}