High inhibitory activity of R 5020, a pure progestin, at the hypothalamic-adenohypophyseal level on gonadotropin secretion.
Synthetic "progestins" currently used in the contraceptive pill inhibited the luteinizing hormone (LH) responsiveness to LH-releasing hormone in cells in culture in a way undistinguishable from that of androgens. Moreover, they competed for binding of the 3H-labeled androgen R 1881 to the rat prostate androgen receptor and stimulated seminal vesicle and prostate weight in castrated rats. R 5020, a pure progestin, was without effect on the above-mentioned parameters. However, a complete inhibition of the LH surge measured in the afternoon of expected proestrus was obtained at a dose of R 5020 similar to that of D-norgestrel. The synthetic progestin was also found to inhibit ovulation and to delay vaginal cornification. The present data show that the synthetic "progestins" commonly used in the pill possess intrinsic androgenic activity which could well be responsible, to an unknown extent, for their effectiveness as contraceptive agents. R 5020, a synthetic progestin devoid of androgenic activity, is at least as potent as the most potent 19-nortestosterone derivative, D-norgestrel, in inhibiting gonadotropin secretion and other parameters of the estrous cycle in the rat. The availability of a pure progestin devoid of androgenic activity but highly effective as an inhibitor of gonadotropin secretion could be of great interest for the development of an improved contraceptive.
D000818:Animals; D002478:Cells, Cultured; D002715:Chlormadinone Acetate / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D008525:Medroxyprogesterone / Q000494:pharmacology; D008535:Megestrol / Q000494:pharmacology; D009277:Nandrolone / Q000031:analogs & derivatives / Q000494:pharmacology; D009644:Norgestrel / Q000494:pharmacology; D010060:Ovulation / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000187:drug effects*; D011374:Progesterone / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology*; D011467:Prostate / Q000378:metabolism; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D014621:Vagina / Q000187:drug effects
D045167:Progesterone Congeners; D011944:Receptors, Androgen; D002715:Chlormadinone Acetate; D007987:Gonadotropin-Releasing Hormone; D009644:Norgestrel; D011374:Progesterone; D009277:Nandrolone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D008535:Megestrol; D008525:Medroxyprogesterone