Knox K L, Ringstrom S J, Szabo M, Perlyn C A, Sutandi S, Schwartz N B
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA.
Endocrinology. 1996 Apr;137(4):1226-32. doi: 10.1210/endo.137.4.8625893.
We used passive immunization with an antiserum to the alpha-subunit of inhibin (anti-I) or acute ovariectomy to investigate the relationship between serum inhibin levels and FSH secretion in the presence of the progesterone/glucocorticoid antagonist RU486. We demonstrated previously that 1) anti-I administered at 1700 h causes serum FSH to rise on the morning of estrus, even in the presence of a GnRH antagonist, when the two treatments are delivered on proestrus; and that 2) RU486 given on proestrus (1230 h), a time when serum estradiol levels are high, not only blocks the natural secondary FSH surge, but also suppresses the anti-I-induced rise in serum FSH on the morning of estrus. We have now extended our studies of the relationship between inhibin and RU486 to investigate treatment with RU486 and anti-I on a different day of the cycle, estrus, when serum estradiol levels are low. When both RU486 and anti-I were given on estrus (1230 and 1700 h, respectively), RU486 failed to block the anti-I-induced rise in serum FSH on the next morning of metestrus, in contrast to the blockade seen with RU486 treatment on the day of proestrus. However, pretreatment with estradiol benzoate (50 microgram) on the evening of proestrus, before the RU486 and anti-I treatment on estrus, caused RU486 to suppress the effects of anti-I on serum FSH, as it does when given on proestrus. We then repeated the study, using ovariectomy on proestrus or estrus (1700 h) to raise serum FSH, and assessed the effects of RU486 treatment at proestrus and estrus and estradiol benzoate treatment on proestrus. Our results indicate that treatment with RU486 can block the postovariectomy rise in serum FSH only in the presence of high circulating estradiol levels. We conclude that the inhibitory action of RU486 on FSH secretion after a fall in serum inhibin depends on a precedent estradiol background, probably due to induction of progesterone receptors by estradiol.
我们使用抗抑制素α亚基抗血清（抗 - I）进行被动免疫或急性卵巢切除术，以研究在存在孕酮/糖皮质激素拮抗剂RU486的情况下血清抑制素水平与促卵泡激素（FSH）分泌之间的关系。我们之前证明：1）在发情前期同时给予促性腺激素释放激素（GnRH）拮抗剂和在17:00给予抗 - I，即使存在GnRH拮抗剂，在发情日早晨血清FSH仍会升高；2）在发情前期（12:30）给予RU486，此时血清雌二醇水平较高，不仅会阻断自然的继发性FSH高峰，还会抑制发情日早晨抗 - I诱导的血清FSH升高。我们现在扩展了对抑制素与RU486之间关系的研究，以探讨在发情期（血清雌二醇水平较低）这一周期的不同日子给予RU486和抗 - I的治疗效果。当在发情期分别于12:30和17:00给予RU486和抗 - I时，与发情前期给予RU486治疗时出现的阻断作用相反，RU486未能阻断在发情后期次日早晨抗 - I诱导的血清FSH升高。然而，在发情前期晚上，在发情期给予RU486和抗 - I之前，先用苯甲酸雌二醇（50微克）预处理，会使RU486像在发情前期给予时那样抑制抗 - I对血清FSH的作用。然后我们重复该研究，在发情前期或发情期（17:00）进行卵巢切除术以升高血清FSH，并评估发情前期和发情期给予RU486治疗以及发情前期给予苯甲酸雌二醇治疗的效果。我们的结果表明，只有在循环雌二醇水平较高时，给予RU486才能阻断卵巢切除术后血清FSH的升高。我们得出结论，血清抑制素水平下降后，RU486对FSH分泌的抑制作用取决于先前的雌二醇背景，这可能是由于雌二醇诱导了孕酮受体。
