NONCOMPETITIVE ANTIESTROGENIC ACTIVITY OF PROGESTERONE ANTAGONISTS INPRIMATE MODELS

We have summarized some of the studies containing basic biological dat a suggesting potential therapeutic utility of the antiproliferative ac tivity of antiprogestins on uterine tissues. The non-competitive anti- oestrogenic effects of RU486 were examined using oestradiol-treated ov ariectomized monkeys given RU486, progesterone or both. The oestradiol -induced luteinizing hormone surge of control animals was abrogated by progesterone and/or RU486. Secretory transformation by progesterone w as inhibited by RU486 co-administration. RU486 alone (1 mg/kg) induced endometrial secretory transformation, but higher doses (5 mg/kg) indu ced inhibited proliferation and secretory activity. Thus, in the prese nce of progesterone, RU486 is antagonistic but, in its absence, RU486 exhibits endometrial progestational effects at low doses and an anti-p roliferative (anti-oestrogenic) effect at higher doses. These data enc ourage continued evaluation of RU486 as a potential contraceptive agen t acting at the pituitary and/or endometrial level. Our study also dem onstrates that after physiological oestradiol replacement therapy, oes tradiol receptor concentrations rise dramatically following antiproges tin treatment; this effect was dose-dependent.