The seminiferous epithelium of the Brown Norway rat gradually looses germ cells as the animals advance from 12 to 24 months of age. This loss occurs in the absence of disease, obstruction of the reproductive tract or substantial changes in serum FSH or intratesticular testosterone concentrations. However, concomitant with loss of gem cells are specific changes in gene expression by the somatic Sertoli cells. While testis content of SGP-2 mRNA is constant from 6-24 months, testis content of transferrin mRNA increases. Testicular aging may therefore result in part from changes inherent to Sertoli cells. This proposal explores this proposition by examining the effect of aging on the responses of Sertoli cells to germ cells and to hormones. Additionally, we explore whether aging-related loss of Sertoli cell function can be prevented. These objectives are addressed in 3 specific aims. First, we examine the effects of aging on germ cell-Sertoli cell interactions. We explore whether the stage-specific expression of CP-2 mRNA is degraded during aging and determine whether aging reduces the capacity of germ cells to alter gene expression of Sertoli cells in vitro. Second, we examine whether aging alters the responsiveness of Sertoli cells in vitro to FSH, insulin and EGF, all modulators of the function of immature or mature Sertoli cells. Third, we determine whether age-related changes in Sertoli cell function can be prevented by altering the endocrine status of the aging animal.