Chronic alcoholic males often exhibit a spectrum of sexual dysfunction. These men are frequently hypogonadal and generally have low serum testosterone levels. In addition, these men are often feminized, in spite of relatively normal serum estrogen levels. These hormones exert their influence at the cellular level by interactions with highly specific proteins, the hormone receptors. Our work to date has shown that rats fed alcohol chronically have significant alterations in hepatic content of both androgen and estrogen receptors as well as alterations in hormone-related hepatic function. Those animals fed alcohol have reduced hepatic androgen receptor levels, and show a parallel reduction in two hepatic androgen responsive proteins. Further, these animals demonstrate enhanced hepatic content of estrogen receptors, thus increasing the estrogen sensitivity of that tissue, a finding which helps explain how feminization can occur even in the absence of elevated serum estrogens. The research outlined in this proposal addresses the mechanism for control of the level of hepatic androgen and estrogen receptors. The work focuses on the liver because that organ metabolizes sex steroids in a sexually dimorphic manner; alterations in serum testosterone and other factors can result in shift of the pattern of hepatic hormone metabolism from a masculine to a feminine pattern, thus compromising further the sexual integrity of the male. Experiments will address specifically the control of sex steroid metabolism and sex steroid receptor levels in the liver by sexually dimorphic patterns of growth hormone release. It will be determined how alcohol feeding of the male rat alters growth hormone release and correlate these alterations with the changes in hepatic hormone metabolism and receptor levels. Other experiments will attempt to reverse these changes by administration of appropriated sex hormone therapy. Later experiments will be performed to define the temporal relationship and the reversibility of such changes. The results of this research will provide a basis for understanding the mechanisms responsible for feminization of the adult male alcoholic.
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