Effect of RU486 on ovarian progesterone production at pro-oestrus and during pregnancy: a possible dual regulation of the biosynthesis of progesterone.

Changes in progesterone production were analysed after intrabursal ovarian administration of the antiprogesterone RU486, mifepristone, in rats at pro-oestrus and during pregnancy. RU486 was administered at 09:00-10:00 h and serum progesterone was measured 8 h after treatment, except for those on days 3 and 12 of pregnancy when the steroid was measured 4, 8 and 24 h later. RU486 stimulates progesterone production on the day of pro-oestrus and on days 3-5 and 15-20 of pregnancy. Conversely, treatment with the antiprogestagen inhibits progesterone production on days 7-14 of gestation. The inhibition (day 12) or stimulation (day 19) of progesterone production induced by RU486 could be correlated with the simultaneous inhibition or stimulation of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity observed in corpora lutea. A similar effect on 3 beta-HSD activity in corpora lutea was obtained by intrabursal ovarian administration of a specific progesterone antibody, indicating that the effect of RU486 is exerted through its antiprogesterone action. On the day of pro-oestrus and during early pregnancy the intrabursal ovarian injection of RU486 did not modify serum prolactin and LH concentrations, demonstrating that the antiprogesterone did not have a central action. The stimulatory action of RU486 on progesterone production on days 3 and 5 of pregnancy shifted to an inhibitory effect on progesterone production on day 7. Oestradiol treatment on day 6 of pregnancy reversed the effect of RU486 on progesterone production on day 7, inducing a response similar to that obtained on days 3 and 5 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)