Inhibition of ovulation in rats with epostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase.
Epostane (Win 32729), an inhibitor of the 3 beta-hydroxysteroid dehydrogenase enzyme system, inhibited both spontaneous and pregnant mare's serum/human chorionic gonadotropin-induced ovulation in rats. When administered on the morning of proestrus, the drug blocked pregnancy in females that were inseminated that evening. The blockage of pregnancy occurred at a dose of 200 mg/kg but not at 50 mg/kg. Similarly, when administered on the morning of proestrus at a dose of 200 mg/kg, epostane inhibited the appearance of ova in the oviducts the next day. In gonadotropin-primed immature rats, epostane inhibited ovulation in a dose-related fashion with an ED50 between 25 and 50 mg/kg. The drug also decreased plasma progesterone levels in these animals. The inhibitory effect of epostane on gonadotropin-stimulated ovulation was reversed by injections of progesterone at a total daily dose of 6.25 mg/rat or greater. These results support the contention that steroidogenesis, specifically progesterone synthesis, is a prerequisite to ovulation.
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003271:Contraceptive Agents, Female; D013196:Dihydrotestosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology; D010060:Ovulation / Q000187:drug effects*; D011247:Pregnancy; D011359:Proestrus; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D006063:Chorionic Gonadotropin; D003271:Contraceptive Agents, Female; D006064:Gonadotropins, Equine; D013196:Dihydrotestosterone; D011374:Progesterone; C033264:4,17-dimethyltrilostane; D015096:3-Hydroxysteroid Dehydrogenases