ANDROGEN MODULATION OF FOLLICLE-STIMULATING HORMONE-INDUCED GRANULOSA CELL STEROIDOGENESIS IN THE PRIMATE OVARY.

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Abstract
The role of androgen in regulating FSH-induced steroidogenesis in primates was investigated in granulosa cell cultures from reproductively suppressed (acyclic) marmoset monkeys. Progesterone accumulation and induction of aromatase activity were measured during a 48-h culture of granulosa cells (isolated from 0.5-1.0 mm diameter follicles) in medium 199 containing human (h) FSH and/or various sex steroids. Steroidogenesis in control cultures was minimal, but the presence of hFSH (0.3-100 ng/ml) caused dose-dependent stimulation. Maximal responses (mean .+-. SE) were observed with 30 ng/ml of hFSH (aromatase, 1.0 .+-. 0.2 pmol estradiol/103 cells .cntdot. 3 h; progesterone, 4.5 .+-. 0.8 pmol/103 cells .cntdot. 48 h) and were 100 times basal values. The presence of testosterone (10-6 M) during the 48-h culture enhanced the responses to hFSH two- to six-fold over the range 0.3-3.0 ng hFSH/ml. In the presence of a submaximal stimulatory dose of hFSH (3 ng/ml), the effects of testosterone on granulosa cell steroidogenesis were dose-related. Maximum responses were obtained with doses of testosterone between 10-8 and 10-7 M. Similar dose-dependent effects were found with 5.alpha.-dihydrotestosterone (a non-aromatizable androgen), but not with estradiol, suggesting specific androgen synergism with FSH. Maximal aromatase activity induced after in vitro treatment with hFSH approached that in granulosa cells freshly isolated from a preovulatory follicle of a cyclic animal. These results demonstrate steroid modulation in vitro of FSH-responsive function, similar to that observed in rodent granulosa cells. Therefore, androgen may play a local role in the regulation of FSH-stimulated granulosa cell function during follicular development in primates.

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