The effect of aging on the male reproductive tract is receiving increasing attention for several reasons. Among these are: 1) the population for the United States is aging rapidly, and thus there is increased interest in geriatric medicine; 2) a number of diseases of aged men (e.g. benign prostatic hyperplasia) are dependent on testicular hormones; 3) there is evidence that some drugs commonly used in elderly men (e.g. Gemfibrozil, a blood cholesterol-lowering drug) cause Leydig cell neoplasia; 4) there is evidence for statistically significant correlation between diminished testosterone production and diminished libido and potency in aged menl; 5) the pharmacologic effects of a number of drugs have been shown to change with aging; and 6) diseases of endocrine origin such as osteoporosis are likely to become major problems in geriatric male. In this program project application, we will determine whether age- related changes in the rat male reproductive tract result exclusively from changes in somatic cells extrinsic to the testis, ro whether there also are deleterious age-associated changes intrinsic to Leydig, Sertoli and germ cells. We also will examine how age affects androgen control of biologic functions associated with the prostate gland. To accomplish these objectives, we present five highly integrated research projects. In Project 1, Dr. Ewing will examine the effect of aging on the structure and function of the Leydig cell the cell within the testis that produces testosterone. Dr.Zirkin, in Project 2, will examine the possible consequences of age-associated changes in Leydig cells by studying the morphologic response of proliferating, meiotic and differentiating ells of the seminiferous tubules of aging rats to changes in intratesticular testosterone concentration. In Project 3, Dr. Wrights will examine to effect of aging and of changes in testicular testosterone on Sertoli cells and testicular stem cells. Dr. McCarrey, in Project 4, will examine age-associated changes in spermatogenic cell gene expression, and so will focus on the consequences of aging on spermatogenic cell function. Finally, Dr. Brown, in Project 5, will examine the effect of aging o androgen control of the rat prostate, a sex accessory organ that is exquisitely sensitive to androgen changes.
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