Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotropin (hCG) are glycoproteins that are similar in structure to TSH. Glycosylation is not identical among the different hormones, and the type of glycosylation influences the halflife of the hormones. A sulfated ^-acetylgalactosamine attached to LH but not FSH causes LH to be more rapidly metabolized; the half-life of LH is 30 minutes and that of FSH is 8 hours.
LH and FSH are pituitary hormones secreted in pulsatile fashion approximately every 2 hours. In women before menopause, this pattern is superimposed on much larger changes that occur during the normal menstrual cycle. FSH is released in substantial amounts during the follicular phase of the menstrual cycle and is required for proper development of ovarian follicles and for estrogen synthesis from granulosa cells of the ovary. Most LH secretion occurs in an abrupt burst just before ovulation. LH is required for progesterone synthesis in luteal cells and androgen synthesis in thecal cells of the ovary. FSH stimulates spermatogenesis and synthesis of androgen-binding protein in Sertoli cells of the testes. LH stimulates testosterone production from Leydig cells. Production of LH and FSH is controlled by gonadotropin-releasing hormone (GnRH) from the hypothalamus and by feedback control from target organs through steroids and multiple forms of a protein, in-hibin.
Injections of these hormones are used to treat infertility in women and men. Traditional sources of gonadotropins are from human urine. Human menopausal gonadotropins (menotropins, Humegon, Pergonal) are isolated from urine of postmenopausal women and contain both FSH and LH. Purified preparations of FSH from the same source are also available (urofollitropin, Fertinex, Fertinorm HP). During early pregnancy, trophoblasts of the placenta produce hCG in large amounts. LH and hCG bind to the same go-nadal receptors, but hCG is more stable and can be isolated from urine of pregnant women, so hGH preparations (Pregnyl, Profasi) are used to mimic the burst of LH secretion before ovulation. Recombinant preparations of FSH are also available (follitropin, Gonal F, Follistim).
Gonadotropins are used to treat infertility in women with potentially functional ovaries who have not responded to other treatments. The therapy is designed to simulate the normal menstrual cycle as far as is practical. A common protocol is daily injections of menotropins for 9 to 12 days, until estradiol levels are equal to that in a normal woman, followed by a single dose of hCG to induce ovulation. Two problems with this treatment are risks of ovarian hyperstimulation and of multiple births. Ovarian hyperstimulation is characterized by sudden ovarian enlargement associated with an increase in vascular permeability and rapid accumulation of fluid in peritoneal, pleural, and pericardial cavities. To prevent such occurrences, ovarian development is monitored during treatment by ultrasound techniques and by measurements of serum levels of estradiol.
Purified FSH is used to prepare follicles for in vitro fertilization because LH activity in menotropins may cause premature ovulation. Purified FSH is also used to treat infertility in women with polycystic ovarian disease; in this disease LH and androgen production may already be elevated.
Gonadotropins are used to induce spermatogenesis in hypogonadotropic hypogonadal men; a lengthy treatment is required to obtain mature sperm. For several weeks hCG is injected to increase testosterone levels, followed by injections of menotropins for several months. Prepubertal cryptorchidism can be treated by injections of hCG for up to several months.
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