Contraceptive potential of RU 486 by ovulation inhibition: II. Suppression of pituitary gonadotropin secretion in vitro.
That the antiprogestin RU 486 delays or inhibits the LH surge, and induces premature luteolysis in monkeys and women concurrent with a reduction in LH/FSH secretion has been reported. Whether this inhibition of gonadotropin release was a result of action at the hypothalamic and/or pituitary level is unknown. Here, we utilized a rat pituitary cell culture system to evaluate direct RU 486 actions on pituitary gonadotropin secretion in vitro. Cell cultures were primed with 10 nM estradiol for 48 h in order to maintain progesterone receptors. Basal and GnRH-induced secretion were evaluated after a 4-hour incubation period. The progesterone antagonist RU 486 inhibited GnRH-induced LH and FSH secretion in a dose-dependent manner, without affecting basal gonadotropin release. This inhibition of gonadotropin secretion was specific and antagonized by addition of progesterone in vitro.
Wolf
J P
JP
Laboratoire D'Histologie-Embryologie-Hôpital Bicêtre, Paris, France.
Danforth
D R
DR
Ulmann
A
A
Baulieu
E E
EE
Hodgen
G D
GD
D000818:Animals; D002478:Cells, Cultured; D003270:Contraceptive Agents / Q000494:pharmacology*; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D015735:Mifepristone; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010906:Pituitary Hormone-Releasing Hormones / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D003270:Contraceptive Agents; D004963:Estrenes; D010906:Pituitary Hormone-Releasing Hormones; D015735:Mifepristone; D011374:Progesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone