Laufer N, Reich R, Braw R, Shenker J G, Tsafriri A
Biol Reprod. 1982 Sep;27(2):463-71. doi: 10.1095/biolreprod27.2.463.
The effect of clomiphene citrate was tested on rat preovulatory follicles in culture. Clomiphene inhibited both basal and luteinizing hormone (LH)-stimulated steroid accumulation. The dose-dependent effect of clomiphene was much more pronounced on follicles cultured with LH; while 0.01 mM had no effect, 2 mM clomiphene decreased progesterone accumulation by 97%, estradiol-17 beta by 90% and testosterone by 65% (P less than 0.001). The inhibitory action of the drug was not prevented by addition of 8-Br-cAMP (1 mM) or pregnenolone (1 microgram/ml) to the culture medium. clomiphene (0.01 - 0.5 mM) induced the resumption of meiotic maturation even in LH-free medium in approximately 60% of follicle-enclosed oocytes. At the higher concentrations tested (0.1 - 0.5 mM) degenerative changes were noted in a high proportion of oocytes (30-40%). Follicles incubated for 24 h with clomiphene exhibited dose-dependent atretic-like changes. These effects of clomiphene on preovulatory follicles may account for the discrepancy between ovulation and pregnancy rates observed in women treated with clomiphene.
在体外培养条件下，检测了枸橼酸氯米芬对大鼠排卵前卵泡的作用。氯米芬抑制基础状态以及促黄体生成素（LH）刺激的类固醇积累。氯米芬的剂量依赖性作用在用LH培养的卵泡上更为明显；0.01 mM时无作用，2 mM氯米芬可使孕酮积累减少97%，雌二醇-17β减少90%，睾酮减少65%（P<0.001）。向培养基中添加8-溴环磷酸腺苷（1 mM）或孕烯醇酮（1微克/毫升）并不能阻止该药物的抑制作用。即使在无LH的培养基中，氯米芬（0.01 - 0.5 mM）也能使大约60%的卵泡包绕卵母细胞恢复减数分裂成熟。在较高测试浓度（0.1 - 0.5 mM）下，则有高比例（30 - 40%）的卵母细胞出现退行性变化。用氯米芬孵育24小时的卵泡呈现出剂量依赖性的闭锁样变化。氯米芬对排卵前卵泡的这些作用可能解释了在接受氯米芬治疗的女性中观察到的排卵率与妊娠率之间的差异。
