The role of androgens in follicular development in the ovary. I. A quantitative analysis of oocyte ovulation.

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.