Androgen modulation of follicle-stimulating hormone-induced granulosa cell steroidogenesis in the primate ovary.
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/10(3) cells X 3 h; progesterone, 4.5 +/- 0.8 pmol/10(3) cells X 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.
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D002143:Callitrichinae; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D013739:Testosterone / Q000494:pharmacology
D000728:Androgens; D013256:Steroids; D013196:Dihydrotestosterone; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D001141:Aromatase