Stimulatory Action of Follicle-Stimulating Hormone and Androgens on the Responsiveness of Rat Granulosa Cells to Gonadotropins in Vitro**

Abstract

This paper describes experiments on cultured rat granulosa cells designed to test the effects of chronic FSH and/ or androgen treatment during culture on the later responsiveness of these cells to acute LH and FSH stimulation; responsiveness of the cells was measured in terms of both cAMP and progesterone production. When compared to control cultures (medium alone), culture of the cells with androgen alone increased the responsiveness of the cells to FSH, but not to LH, stimulation. Culture of the cells with FSH alone enhanced the responsiveness of the cells to both FSH and LH. When the cells were cultured with both FSH and androgen, the acute stimulation with either FSH or LH was further enhanced; analysis of the data showed a synergism between FSH and androgen. Culture of the cells with either 17β-estradiol or progesterone did not alter the responsiveness to LH but increased the responsiveness to FSH to an extent similar to that seen with androgen alone. Aminoglutethimide had no significant effect on the responsiveness brought about by FSH and androgen, suggesting that the increased responsiveness obtained by culture of the cells with both FSH and androgen is not mediated by endogenous steroid hormones. A comparison of the responsiveness of freshly isolated cells with that of cells cultured with FSH plus androgen showed that, after culture, the capacity of the cells to produce cAMP in response to LH was greatly increased, whereas it was only maintained in response to FSH. These results show that androgens can alter the responsiveness of cultured granulosa cells to gonadotropic hormone stimulation and lend further support to the notion that androgens may play an important role in the maturation of ovarian follicles.