Regulation of Luteinizing Hormone Secretion in Male Sheep by Endogenous Estrogen*

Both androgens and estrogens are implicated in the regulation of gonadotropin secretion in the male. Three experiments were conducted to determine the physiological importance of estradiol (E2) in the feedback regulation of LH secretion in male sheep. In the first experiment, LH secretion in castrate rams (wethers) was shown to be susceptible to the picomolar concentrations of E2 found in intact rams. In the second experiment, aminoglutethimide (AG) was administered to testosterone-implanted wethers to block aromatization of testosterone and ascertain the possible consequences of E2 deprivation on testosterone-mediated LH suppression. AG had no apparent effect on serum testosterone, but reduced serum E2 by half and increased serum LH approximately 3-fold. These data suggest that aromatization of testosterone to E2 is a physiologically important step in the regulation of LH secretion in the ram and that aromatization occurs, at least in part, in peripheral tissues. The relative contributions of peripherally and centrally derived E2 in the regulation of LH remain uncertain. In the third experiment, immunoneutralization of endogenous E2 in intact rams by active immunization against E2 was shown to stimulate pulsatile LH secretion and elevate basal and mean LH concentrations. Associated with this LH response was a significant increase in serum testosterone, such that immunized rams exposed to a nonstimulatory 16-h light, 8-h dark photoperiod had testosterone concentrations equivalent to those of control rams exposed to a stimulatory 8-h light, 16-h dark photoperiod. Together, these findings emphasize the importance of E2 in the control of male reproduction and suggest the possibility of improving year-round reproductive performance of the domestic ram through E2 immunoneutralization.