Androgen deprivation induces phenotypic and functional changes in the thymus of adult male mice

The functional immunological consequences of thymic regeneration after castration were studied in adult male C57B1/6 mice. Phenotypic profiles of thymocytes present in the enlarged thymuses of castrate animals demonstrated a significant decrease in the proportion of thymocytes positive for the suppressor/cytotoxic phenotype (CD4^-CD8⁺; P = 0.005). Thymic enlargement in castrate animals was accompanied by increased capacity of thymocytes to incorporate thymidine in response to Concanavalin A in vitro. Spleens from castrate mice also were enlarged, and in vitro generation of functional suppressor cells by splenocytes from castrate animals was decreased. Testosterone replacement resulted in thymic regression, with a shift toward expression of mature thymocyte phenotypes, a decrease in the double-positive phenotype (CD4⁺CD8⁺), and a relative predominance of the CD4^-CD8⁺suppressor/cytotoxic phenotype over the CD4⁺CD8^-helper phenotype. Unstimulated thymidine incorporation by thymocytes from androgen-treated animals was decreased compared to controls (P = 0.050). Spleen size was not altered by androgen administration. These findings suggest that in the adult animal, changes in androgen status effect alterations in thymocyte phenotypic profiles and thymocyte function, with removal of androgens shifting the T cell balance toward the CD4 helper subset and administration of androgens changing the balance toward CD8 suppressor/cytotoxic T cell predominance.