Previous work by our laboratory and others have shown that chronic ethanol ingestion by sexually immature male mice and rats delays the process of sexual maturation. The work proposed in the present application is aimed at the evaluation of putative mechanisms for this effect, based upon known changes which accompany pubertal development. The effect of chronic ethanol ingestion by male Swiss-Webster mice on maturational changes at the hypothalamic-pituitary, as well as testicular levels will be examined, and compared with those changes which occur in pair-fed controls. At the hypothalamic-pituitary level, the development of the LHRH self-priming effect will be examined, as well as developmental profiles of circulating levels of follicle stimulating hormone. At the testicular level, key maturational changes in Leydig cell development will be examined, including increases in luteinizing hormone receptor numbers and levels of 17 Beta-hydroxysteroid dehydrogenase activity. Alterations in Leydig cell steroidogenic enzyme activities will be correlated with circulating steroidal hormone profiles during pubertal development. Special attention will be given to Sertoli cell maturational changes, based upon the essential role of the Sertoli cell in initiation of spermatogenesis and maintenance of high androgen concentrations in epididymal structures via the secretion of androgen binding protein. Evaluation of Sertoli cells involves ultrastructural analyses, Sertoli cell/Leydig cell interactions, FSH-binding and response, and measurement of the integrity of the blood-testis barrier. Differences in the above-mentioned variables as a function of development due to ethanol treatment will be evaluated by analysis of variance. Possible cause-effect relations to delayed sexual maturation will be identified through correlational analyses with indices of reproductive function (e.g., testicular weights and function, spermatogenesis, fertilizing ability of spermatozoa). Alcohol abuse among adolescents remains a serious problem in this country. consequences of delayed sexual maturation are substantial. The stigma associated with reproductive incompetence would likely represent a stimulus for more intensive drinking by the young male alcoholic, contributing further to his poor physiological condition. The proposed work is directed toward a better understanding of the potential for reproductive impairment among adolescent alcoholics, as well as the mechanisms by which such impairment may occur.
