Prepubertal orchidectomy induces thymic abnormalities in aging (NZB X SJL)F1 male mice.

Female but not male (NZB X SJL)F1 (NS) mice develop abnormalities of their intrathymic lymphocyte population in the course of aging. To determine the role played by androgens in this sex-related difference, we monitored the evolution of the cellular composition of the thymus in NS males deprived of androgens by prepubertal orchidectomy. Although in young mice this operation resulted in a twofold enlargement of the thymus, there was no histologic alteration or major change in the surface phenotype and mitogenic reactivities of the thymocytes, which suggests that all thymocyte subsets were increased to the same extent. In 12-mo-old control (BALB/c X SJL)F1 mice, prepubertal orchidectomy also produced an equal expansion (1.4-fold increase) of all thymocyte subsets. In contrast, in 12-mo-old orchidectomized NS males, there was a marked depletion of the thymic cortex and a hyperplasia of the medullary lymphoid tissue reflecting the selective expansion of a subset of phenotypically mature T cells (dull Thy-1+, Lyt-1+2+/-, dull PNA+) together with the emergence of intrathymic surface immunoglobulin-bearing cells. These latter cells probably represented B cells because there was a concomitant augmentation of the mitogenic responsiveness in vitro of thymic cell suspensions to lipopolysaccharide. Such thymic abnormalities induced by prepubertal orchidectomy in old NS males resemble those occurring spontaneously in the NS females. This suggests that the absence of thymic disease in intact NS males is primarily due to a suppressive effect of androgens.