Ware V C
J Exp Zool. 1982 Aug 10;222(2):155-67. doi: 10.1002/jez.1402220207.
In an attempt to understand more fully processes that control the selection or recruitment of follicles for ovulation, the superovulation paradigm in combination with the androgen, 5 alpha-dihydrotestosterone, or the antiandrogens, cyproterone or cyproterone acetate, was used in the immature mouse to alter the developmental potential of follicles destined to ovulate or to become atretic. Quantitative analysis of the numbers of eggs ovulated after one or more rounds of stimulation by pregnant mare's serum gonadotrophin followed by human chorionic gonadotrophin (PMSG-hCG), revealed a dose-dependent ovulation response to exogenous androgen and antiandrogen. Low dosages of androgen improved the ovulation response significantly. Large dosages of cyproterone and cyproterone acetate (100 mg/kg body weight) generally decreased the ovulation number in gonadotrophin-injected mice, suggesting a role for androgen in preovulatory events that occur within the ripened follicle after the ovulatory stimulus (hCG) has been received. Low dosages of cyproterone, particularly 25 mg/kg, significantly enhanced the ovulatory response, a phenomenon not observed for cyproterone acetate at this dosage. Radioimmunoassays of serum LH suggested that the differential response of the ovary to the two antiandrogens was probably related to endogenous LH release. Experiments in which the time of administration of hCG +/- cyproterone was varied after PMSG priming suggested that cyproterone at a dosage of 25 mg/kg had a "rescuing" effect on follicles destined to become atretic for up to 96 hr after PMSG priming. Cyproterone at a dosage of 100 mg/kg had no such effect, and actually decreased the magnitude of the ovulatory response at all time points tested, suggesting that follicular atresia was accelerated by this treatment. Experiments in which the time of administration of cyproterone (100 mg/kg) was varied after hCG suggested that whatever the important androgen-mediated events preceding ovulation, these events occur within 2 to 3 hr after the hCG signal. By quantitating the numbers of eggs over several superovulation cycles, it could be shown that hormonal treatment in one induced cycle could affect significantly the ovulation response in subsequent cycles, suggesting that androgens influence the development of classes of follicles other than preovulatory follicles. These studies suggest that the process through which follicles are selected for ovulation is extremely sensitive to the androgenic environment and that the developmental pathways leading to ovulation or preovulatory follicular atresia are closely linked.
为了更全面地了解控制卵泡选择或募集以进行排卵的过程，在未成熟小鼠中使用超排卵模式并结合雄激素5α-二氢睾酮或抗雄激素药物醋酸环丙孕酮或环丙孕酮，以改变注定要排卵或闭锁的卵泡的发育潜能。对用孕马血清促性腺激素随后用人绒毛膜促性腺激素（PMSG-hCG）进行一轮或多轮刺激后排卵的卵子数量进行定量分析，结果显示对外源性雄激素和抗雄激素存在剂量依赖性的排卵反应。低剂量的雄激素显著改善了排卵反应。大剂量的环丙孕酮和醋酸环丙孕酮（100mg/kg体重）通常会降低注射促性腺激素的小鼠的排卵数，这表明雄激素在接受排卵刺激（hCG）后成熟卵泡内发生的排卵前事件中发挥作用。低剂量的环丙孕酮，特别是25mg/kg，显著增强了排卵反应，而在此剂量下醋酸环丙孕酮未观察到这种现象。血清促黄体生成素（LH）的放射免疫分析表明，卵巢对这两种抗雄激素的不同反应可能与内源性LH释放有关。在PMSG预处理后改变hCG±环丙孕酮给药时间的实验表明，25mg/kg剂量的环丙孕酮对注定要闭锁的卵泡在PMSG预处理后长达96小时具有“挽救”作用。100mg/kg剂量的环丙孕酮没有这种作用，实际上在所有测试时间点都降低了排卵反应的幅度，这表明这种处理加速了卵泡闭锁。在hCG后改变环丙孕酮（100mg/kg）给药时间的实验表明，无论排卵前重要的雄激素介导事件是什么，这些事件都发生在hCG信号后的2至3小时内。通过对几个超排卵周期的卵子数量进行定量分析，可以发现一个诱导周期中的激素处理会显著影响后续周期的排卵反应，这表明雄激素会影响除排卵前卵泡之外的其他类卵泡的发育。这些研究表明，卵泡被选择用于排卵的过程对雄激素环境极其敏感，并且导致排卵或排卵前卵泡闭锁的发育途径紧密相连。
