Stimulatory Action of Androgen Administration in Vivo on Ovarian Responsiveness to Gonadotropins*

Abstract
In intact immature female rats, ovarian progesterone levels were significantly elevated 1 h after iv injection of either LH (NIH-LH-B8, 10 μg) or FSH (NIH-FSH-S11; 100 μg). Testosterone treatment (5 mg daily, sc) for 3 consecutive days enhanced this ovarian progesterone response to LH or to FSH. 17β-Estradiol (1 mg daily for 3 days) had no effect on stimulation of ovarian progesterone production by LH. Although 17β-estradiol slightly enhanced ovarian progesterone levels in response to FSH stimulation, its effect was significantly less than that of testosterone. By contrast, 17β-OH-5α-androstan-3-one (DHT), when administered systemically (10 mg, sc), had no effect on the ovarian responsiveness to either LH or FSH. However, when DHT was administered by means of Silastic minicapsules implanted locally, ovarian progesterone response to FSH, but not LH, was significantly enhanced when compared to the response in controls. A stimulatory action of androgens on the ovary could be explained, at least in part, by their action on granulosa cells. In vivo treatment of rats with testosterone for 3 days (5 mg, sc) significantly enhanced progesterone production by isolated granulosa cells, 1 h after in vitro stimulation by either purified LH or FSH, and significantly enhanced cAMP production by LH, but not FSH. The responsiveness of isolated granulosa cells to LH was also enhanced by in vivo treatment with DHT (10 mg, sc), although to a lesser extent than with testosterone. Responsiveness of these cells to LH was not affected by in vivo treatment with 17β-estradiol (1 mg, sc). In hypophysectomized immature female rate, administration of testosterone failed to alter the responsiveness of the ovaries to LH and inhibited the FSH-induced production of progesterone. Thus, it is proposed that another factor(s) from the pituitary may be required for the observed stimulatory action of androgens on the responsiveness of the ovary in vivo.