The objectives of this study are to search for the mechanism(s) by which ethanol causes male reproductive dysfunctions. Ethanol is known to cause a decrease in circulating gonadotropins and impaired synthesis and secretion of testosterone. It is considered to be very important to determine if ethanol interferes with normal reproductive functions by affecting androgen receptor mechanism. Thus, the proposed research is designed to determine whether chronic exposure to ethanol; 1) disrupts androgen uptake and retention in the cells of the target tissues, 2) depresses androgen-binding to its receptors in the seminiferous tubular elements in the testes, impairing normal reproductive function, 3) has an adverse effect on the regulation of androgen receptors in the pituitary and hypothalamus, modifying the negative feedback control of gonadotropin secretion, and 4) disrupts the structural architecture of gonadotropin secreting cells in the pituitary gland, resulting in a decrease in gonadotropin secretion. Cytosol androgen receptor sites will be determined by sucrose density gradient and charcoal absorption assay. Any ethanol-induced alterations of the androgen receptor sites in the pituitary glands, hypothalamus, and brain cortex will be compared with a possible change of the feedback regulation of gonadotropin secretion. Serum LH levels will be determined by radioimmunoassay. Using the transmission electron microscope, an attempt will be made to correlate ethanol-induced ultrastructural alterations in the gonadotropin secreting cells of the pituitary with changes in the secretion of LH. This study will clarify the biochemical mechanism(s) involved in the pathogenesis of alcohol-induced toxicity and identify the action of alcohol on androgen receptors in various target organs, causing hypothalamic-pituitary-gonadal axis dysfunction and thus devise rationale, based on the results obtained, for effective therapeutic and preventive measures to be used on those who are sterile and/or exhibit an abnormal reproductive capacity resulting from heavy alcohol drinking.
