The effect of aging on testicular function has received increasing attention because diseases such as benign prostatic hyperplasia are major health problems in aged men, because some drugs (e.g. Cemfibrozil; a blood cholesterol lowering drug) causes Leydig cell neoplasia in laboratory animals and because the population of the United States is aging rapidly. We propose experiments which are designed to : first, confirm or refute the reported effect of age on Leydig cell number by a recently developed unbiased stereologic method (Disector method); second, an ultrastructural sterologic analysis (e.g. measure surface area of smooth endoplasmic reticulum) coupled with measurement of testosterone production by in vitro perfused testes will be completed to show unequivocally whether Leydig cells in aged rats are undamaged, atrophied or hypertrophied; third, we will show unequivocally whether the reversal of Leydig cell testosterone production by hCG treatment of aged rats is accomplished by stimulation of already present but regressed Leydic cells or by stimulation of a new population lf Leydig cells; fourth, we will demonstrate whether aging alters the dose of ethylene dimethanesulphonate required to kill rat Leydig cells. We will differentiate between age-related changes in metabolic clearance rate and endogenous sensitivity. Fifth, we will use ethylene dimethanesulphonate as an experimental tool to eliminate Leydig cells from aged rat testes and than whether aging alters the rate or extent of Leydig cell repopulation of the rat tests.
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