Hodgen G D, van Uem J F, Chillik C F, Danforth D R, Wolf J P, Neulen J, Williams R F, Chwalisz K
Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk 23507.
Hum Reprod. 1994 Jun;9 Suppl 1:77-81. doi: 10.1093/humrep/9.suppl_1.77.
We have summarized some of the studies containing basic biological data suggesting potential therapeutic utility of the anti-proliferative activity of antiprogestins on uterine tissues. The non-competitive anti-oestrogenic effects of RU486 were examined using oestradiol-treated ovariectomized 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 was inhibited by RU486 co-administration. RU486 alone (1 mg/kg) induced endometrial secretory transformation, but higher doses (5 mg/kg) induced inhibited proliferation and secretory activity. Thus, in the presence of progesterone, RU486 is antagonistic but, in its absence, RU486 exhibits endometrial progestational effects at low doses and an anti-proliferative (anti-oestrogenic) effect at higher doses. These data encourage continued evaluation of RU486 as a potential contraceptive agent acting at the pituitary and/or endometrial level. Our study also demonstrates that after physiological oestradiol replacement therapy, oestradiol receptor concentrations rise dramatically following antiprogestin treatment; this effect was dose-dependent.
我们总结了一些包含基础生物学数据的研究，这些数据表明抗孕激素对子宫组织的抗增殖活性具有潜在的治疗作用。使用接受雌二醇治疗的去卵巢猴子，给予RU486、孕酮或两者，研究了RU486的非竞争性抗雌激素作用。孕酮和/或RU486消除了对照动物中雌二醇诱导的促黄体生成素激增。联合使用RU486可抑制孕酮诱导的分泌转化。单独使用RU486（1毫克/千克）可诱导子宫内膜分泌转化，但更高剂量（5毫克/千克）可抑制增殖和分泌活性。因此，在有孕酮存在时，RU486具有拮抗作用，但在无孕酮时，RU486在低剂量时表现出子宫内膜孕激素作用，在高剂量时表现出抗增殖（抗雌激素）作用。这些数据促使人们继续评估RU486作为一种可能作用于垂体和/或子宫内膜水平的避孕药物。我们的研究还表明，在进行生理性雌二醇替代治疗后，抗孕激素治疗后雌二醇受体浓度会显著升高；这种效应具有剂量依赖性。
