Abstract
We examined the effects of antiprogesterone steroid RU486 (17β-hy-droxy-11 β- [4-dimethylamino-phenyl] -17α- [1 propynyl] -estra-4, 9-diene-3-one) on human luteal function in vitro. Corpus luteal tissues obtained at gynecological surgery with informed consent and were homogenized and incubated with labeled pregnenolone or testosterone as substrates. The effects of RU486 on 3β-hydroxysteroid dehydrogenase (3β-HSD) activity assessed by the formation of progesterone from pregnenolone, and aromatase activity measured by the conversion of testosteone to estrone and estradiol were examined. Minced corpus luteal tissues were cultured with Medium 199 in a gas phase of O2: CO2at a ratio of 95 : 5 for 1 hour with or without RU486. The concentra-tions of unconjugated- and conjugated pregnenolone, and progesterone from the tissues and media were measured by RIA. RU486 had no effect on 3β-HSD or aromatase activities when 800×g supernatant from corpus luteal tissue was incubated with labeled substrates. When minced tissuee was incubated with RU486, the formation of pregnenolone and progesterone was significantly decreased in both the medium and tissues. These results demonstrated for the first time that the suppression of pregnenolone production by RU486 might be partially due to the inhibition of de novo pregnenolone production in the steroid synthesis in the corpus luteum.
