An intraovarian inhibitory action of estrogen on androgen production in vivo

Abstract

Subcutaneous administration of estradiol-17β (1 mg) to intact, immature female rats for 3 days significantly decreased ovarian androgen levels from 34±7 pg/mg in oil treated control rats to 13±2 pg/mg ovarian tissue. It inhibited ovarian responsiveness to LH, as measured by ovarian androgen, but not as measured by ovarian progesterone concentrations. In oil treated control animals, LH caused an approximately 5-fold increase in ovarian androgen levels, whereas ovarian androgen levels were not stimulated at all by LH in the estrogen treated rats. This inhibitory effect on ovarian androgen response was also demonstrable after 6 h of estrogen treatment. Administraton of estradiol-17β to hypophysectomized immature rats for 3 consecutive days suppressed both ovarian androgen and progesterone levels in response to LH. The cause of the discrepency in the progesterone response between intact and hypophysectomized rats is not clear. However, with regard to the androgen response, it is unlikely that the inhibitory action of estrogen is indirectly mediated by a suppression of endogenous gonadotropin release, since concomitant administration of exogenous gonadotropins failed to alter the estrogen effect. Instead, a direct action on the ovary is suggested by the demonstration that unilateral ovarian estrogen implants exert an inhibitory effect on LH-induced androgen levels in the ipsilateral, but not contralateral, ovary in vivo. These results suggest that in the ovary there exists a local negative feedback loop for the control of testosterone production, in which elevated ovarian estrogen levels suppress ovarian responsiveness to LH stimulation, thereby lowering testosterone production and subsequently decreasing estrogen biosynthesis.