Gonadotrophin inhibition

F5. Fogel, M., and Soffer, L. J., Urinary gonadotrophin-inhibiting substance in Stein-Leventhal sjmdrome and other anovulatory states. Anwr. J. Obstet. Gynecol. 98, 85-91 (1967). 

H6. Hipkin, L. J., Gonadotrophin-inhibiting propertira of tannic acid extracts of human urine. J. Endocrinol. 41, 449-450 (1968). 

Softer, L. J., Salvaneschi, J., and Futterweit, W., A gonadotrophin-inhibiting substance in the urine of normal subjects. J. Clin. Endocrinol. Metab. 22, 532-535 (1962). 

Holtkamp, D.E., Greslin, J.G., Root, C.A. and Lerner, L.J. (1960) Gonadotrophin inhibiting and anti-fecundity effects of chloramiphene. Proceedings of the Society for Experimental Biology and Medicine, 105, 197-201. 

Prolactin is peptide hormone secreted by the pituitary gland. It acts on prolactin receptors in breast tissue where it stimulates production of casein and lactalbu-min. It also acts on the testes and ovaries to inhibit the effects of gonadotrophins. Since the secretion of prolactin is under tonic dopaminergic inhibition by the hypothalamus, dopamine D2-receptor antagonists... 

The explanation for this phenomenon is that in the prepubertal phase the amount of testosterone that is secreted is not sufficient to cause development of the male genitalia, which is normally stimulated by dihydrotestosterone. However, at puberty the secretion of testosterone increases. The increase is large in this syndrome, because lack of dihydrotestosterone decreases the extent of the feedback inhibition of the hormone secretions by the pituitary so that more gonadotrophins are released which stimulate, markedly, the rate of testosterone secretion and hence its concentration in the blood. At these high levels, testosterone has sufficient androgenic effects to stimulate development of the external genitalia. 

These combined contraceptives seem to function by inducing feedback inhibition of gonadotrophin secretion which, in turn, inhibits the process of ovulation (Chapter 8). They also induce alterations in the endometrial tissue that may prevent implantation. Furthermore, the progestogen promotes thickening of the cervical mucus, which renders it less hospitable to sperm cells. This combination of effects is quite effective in preventing pregnancy. 

Danazol is an isoxazole derivative of 17alpha-ethinyl testosterone. It has weak androgenic activity. It inhibits gonadotrophin secretion and is used to suppress ovarian function. It induces endometrial atrophy and has found its major use in the management of endometriosis. Gestrinon has the same indication and acts via a similar mechanism. Danazol has also been used in the management of benign breast disorders such as fibrocystic disease. 

So far no simple equivalent of the oral contraceptive pill has been developed for men. Relatively large doses of testosterone do inhibit gonadotrophin secretion and hence spermatogenesis, and different schedules are under clinical trial at present. 

It inhibits gonadotrophin secretion from pituitary in both men and women thus inhibiting both testicular/ovarian function. 

Hypothalamic amines and the release of gonadotrophins and other pituitary hormones, 8,119 Indane and indene derivatives of biological interest, 4, 163 The Inhibition of nonadrenaline uptake by drugs, 2, 1... 

Androgens (danazol and gestrinone) inhibit secretion of pituitary gonadotrophins. They have androgenic, anti-oestrogenic and anti-progestogenic activity and usually cause amenorrhoea and induce a postmenopausal state. 

Q8 Human chorionic gonadotrophin, which is produced by the implanted blastocyte (developed from the fertilized egg) in the uterus, maintains the corpus luteum and its production of oestrogen and progesterone. This inhibits menstruation therefore implantation of the embryo can occur, and subsequently a placenta can be formed. 

An alternative treatment for endometriosis is danazol. Danazol is a modified progestogen which inhibits production of gonadotrophin it combines androgenic actions with anti-oestrogenic and antiprogestogenic activity. 

For male contraception androgens are under trial they inhibit pituitary gonadotrophin production and have a direct testicular action. 

Mesterolone provides oral therapy its molecular structure is such that its hypothalamic feedback inhibition of pituitary gonadotrophin secretion is less and it does not cause liver injury (see below). 

Some agonist progestogenic activity on hypothalamic receptors, inhibiting gonadotrophin secretion, which also inhibits testicular androgen production. 

Inhibition of ovulation presents a different and easier biological problem. There is no need to suppress continuous formation of the gametes, as in the male, but only to prevent their release from the ovary approximately 13 times a year. Either the pituitary gonadotrophin may be inhibited or the ovary may be made unresponsive to it. 

Combined oestrogen-progestogen oral contraceptives have been extensively used since 1956. The principal mechanism is inhibition of ovulation (4, above) through inhibition of gonadotrophin secretion from the h3 othalamus. In addition the endometrium is altered, so that implantation is less likely (7, above) and cervical mucus becomes more viscous and impedes the passage of the spermatozoa (5, above). 

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