Brenner R M, Slayden O D
Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006.
Hum Reprod. 1994 Jun;9 Suppl 1:82-97. doi: 10.1093/humrep/9.suppl_1.82.
Two experiments were conducted to determine how RU486 affected oestradiol action in the non-human primate female reproductive tract. In the first experiment, spayed rhesus monkeys were first treated with a sequential regimen of oestradiol and progesterone to cause regression and deciliation in the oviduct and progestational development in the endometrium. The ability of oestradiol to stimulate oviductal differentiation and endometrial regeneration in the presence of RU486, progesterone, and progesterone plus RU486 was then tested. RU486 was found to block the ability of oestradiol to increase endometrial growth but did not prevent oestradiol-dependent oviductal differentiation. Also, in the endometrium but not the oviduct, RU486 action differed from simple progesterone withdrawal by causing stromal compaction and glandular apoptosis. In the second experiment, spayed monkeys were first treated with oestradiol for 2 weeks to produce a fully differentiated, ciliated-secretory oviduct and an hypertrophied, proliferative endometrium. The ability of oestradiol to maintain these conditions in oviduct and endometrium during treatment with RU486, progesterone, and progesterone plus RU486 was then tested. It was found that RU486 suppressed the ability of oestradiol to maintain the endometrium in a hypertrophied state but not its ability to maintain the oviduct in a fully ciliated-secretory state. As before, RU486 induced extensive glandular apoptosis and stromal compaction in the endometrium, but not the oviduct. These endometrial effects appeared to be due to a combination of a decrease in proliferation, an increase in epithelial cell death by apoptosis, an increase in stromal compaction and a concomitant decrease in interstitial fluid content, all of which led to a decrease in endometrial wet weight and thickness. These effects of RU486 on oestradiol action were similar in the presence and absence of progesterone and were therefore separate and distinct from the classical antiprogestin effects of RU486. Because RU486 did not inhibit the ability of oestradiol to either stimulate or maintain oviductal differentiation or wet weight, these results suggest that the endometrium is much more sensitive to the anti-proliferative effects of RU486 than the oviducts.
进行了两项实验，以确定RU486如何影响非人类灵长类动物雌性生殖道中的雌二醇作用。在第一项实验中，对摘除卵巢的恒河猴首先给予雌二醇和孕酮的序贯疗法，以导致输卵管退化和脱纤毛，并使子宫内膜发生孕性发育。然后测试了在存在RU486、孕酮以及孕酮加RU486的情况下，雌二醇刺激输卵管分化和子宫内膜再生的能力。结果发现，RU486可阻断雌二醇增加子宫内膜生长的能力，但并未阻止雌二醇依赖性的输卵管分化。此外，在子宫内膜而非输卵管中，RU486的作用与单纯撤去孕酮不同，它会导致基质压实和腺细胞凋亡。在第二项实验中，对摘除卵巢的猴子首先给予雌二醇治疗2周，以产生完全分化的、有纤毛的分泌性输卵管以及肥厚的、增殖性的子宫内膜。然后测试了在使用RU486、孕酮以及孕酮加RU486治疗期间，雌二醇维持输卵管和子宫内膜这些状态的能力。结果发现，RU486抑制了雌二醇将子宫内膜维持在肥厚状态的能力，但并未抑制其将输卵管维持在完全有纤毛的分泌性状态的能力。与之前一样，RU486在子宫内膜而非输卵管中诱导了广泛的腺细胞凋亡和基质压实。这些子宫内膜效应似乎是由于增殖减少、凋亡导致的上皮细胞死亡增加、基质压实增加以及间质液含量随之减少共同作用的结果，所有这些都导致了子宫内膜湿重和厚度的降低。在有或没有孕酮存在的情况下，RU486对雌二醇作用的这些影响都是相似的，因此与RU486的经典抗孕激素作用是分开且不同的。由于RU486并未抑制雌二醇刺激或维持输卵管分化或湿重的能力，这些结果表明，子宫内膜对RU486的抗增殖作用比输卵管更为敏感。
