Yuen B H, Mari N, Duleba A J, Moon Y S
Department of Obstetrics and Gynecology, University of British Columbia, Grace Hospital, Vancouver, Canada.
Fertil Steril. 1988 Apr;49(4):626-31. doi: 10.1016/s0015-0282(16)59830-6.
The effects of clomiphene citrate (CC), 17 beta-estradiol (E2), and human chorionic gonadotropin (hCG) on the accumulation of progesterone (P) and 20 alpha-hydroxy-4-pregnen-3-one (20 alpha-OHP) in cultured human granulosa cells (GC) were examined. In addition, the metabolism of [4-14C]pregnenolone and accumulation of [4-14C]P in response to CC and E2 were determined. The authors conclude the following: (1) the dose-dependent inhibition of P and 20 alpha-OHP production by CC in GC was not reproduced by E2, (2) hCG abolished these effects of CC, (3) these inhibitory actions of CC were not associated with altered 3 beta-hydroxysteroid dehydrogenase activity nor P catabolism indicating that, (4) these actions by CC on the GC occur at some step(s) during steroidogenesis preceding the formation of pregnenolone. These findings may explain, at least in part, the luteal deficiency experienced by women treated with CC, and they also provide a rationale for the use of hCG supplementation during ovulation induction with CC.
研究了枸橼酸氯米芬(CC)、17β-雌二醇(E2)和人绒毛膜促性腺激素(hCG)对培养的人颗粒细胞(GC)中孕酮(P)和20α-羟基-4-孕烯-3-酮(20α-OHP)积累的影响。此外,还测定了[4-14C]孕烯醇酮的代谢以及CC和E2作用下[4-14C]P的积累。作者得出以下结论:(1)E2不能重现CC对GC中P和20α-OHP产生的剂量依赖性抑制作用;(2)hCG消除了CC的这些作用;(3)CC的这些抑制作用与3β-羟基类固醇脱氢酶活性改变或P分解代谢无关,这表明(4)CC对GC的这些作用发生在孕烯醇酮形成之前的类固醇生成的某些步骤。这些发现至少可以部分解释接受CC治疗的女性所经历的黄体功能不足,也为在CC诱导排卵期间使用hCG补充剂提供了理论依据。