Donath J, Nishino Y
Research Laboratories of Schering AG, Berlin, Experimental Oncology, Germany.
J Steroid Biochem Mol Biol. 1998 Aug;66(4):247-54. doi: 10.1016/s0960-0760(98)00033-8.
The present study was undertaken to compare the effects of the pure antiestrogen ZM 182780 (ZM) and the partial agonist tamoxifen (TAM) on ovulation and peripheral hormone levels in the rat. Adult female rats were treated with ZM (5 mg/kg/d) or TAM (5 mg/kg/d) and sacrificed at varying times during the estrous cycle. ZM and TAM were able to inhibit ovulation to nearly the same extent (60% and 70%, respectively). ZM induced a persistent diestrus whereas TAM led to a mixed picture in the vaginal smear. Both antiestrogens suppressed the preovulatory surge of LH, FSH and progesterone but had no effect on basal FSH values. In contrast to TAM, ZM caused an increase in basal levels of LH. Moreover, basal and preovulatory levels of estradiol and androgens were increased by ZM. By contrast, TAM decreased basal and preovulatory values of LH, estradiol, and androgens. These data suggest that ZM inhibits not only the positive but also negative feedback effect of estrogens and TAM seems to inhibit only the positive feedback. Moreover, it is conceivable that the suppressed preovulatory progesterone surge induced by ZM and TAM could be responsible for the antiovulatory effect.
本研究旨在比较纯抗雌激素药物ZM 182780（ZM）和部分激动剂他莫昔芬（TAM）对大鼠排卵及外周激素水平的影响。成年雌性大鼠分别接受ZM（5mg/kg/d）或TAM（5mg/kg/d）处理，并在发情周期的不同时间点处死。ZM和TAM抑制排卵的程度相近（分别为60%和70%）。ZM诱导持续的间情期，而TAM导致阴道涂片出现混合情况。两种抗雌激素药物均抑制促黄体生成素（LH）、促卵泡生成素（FSH）和孕酮的排卵前激增，但对基础FSH值无影响。与TAM不同，ZM导致基础LH水平升高。此外，ZM使雌二醇和雄激素的基础水平及排卵前水平升高。相比之下，TAM降低了LH、雌二醇和雄激素的基础水平及排卵前水平。这些数据表明，ZM不仅抑制雌激素的正反馈作用，还抑制其负反馈作用，而TAM似乎仅抑制正反馈作用。此外，可以想象，ZM和TAM诱导的排卵前孕酮激增受抑制可能是抗排卵作用的原因。
