Androgen receptors in thymic epithelium modulate thymus size and thymocytedevelopment

Castration of normal male rodents results in significant enlargement of the thymus, and androgen replacement reverses these changes. Androgen-resistan t testicular feminization (Tfm) mice also show significant thymus enlargeme nt, which suggests that these changes are mediated by the androgen receptor (AR). The cellular targets of androgen action in the thymus are not known, but may include the lymphoid cells (thymocytes) as well as nonlymphoid epi thelial cells, both of which have been believed to express AR. In the prese nt study immunohistochemical analysis and hormone binding assays were used to demonstrate the presence of AR in thymic epithelial cells. The physiolog ical significance of this epithelial cell AR expression was defined by furt her studies performed in vivo using chimeric mice, produced by bone marrow transplantation, in which AR expression was limited to either lymphoid or e pithelial components of the thymus. Chimeric C57 mice engrafted with Tfm bo ne marrow cells (AR(+) epithelium and AR thymocytes) had thymuses of normal size and showed the normal involutional response to androgens, whereas chi meric Tfm mice engrafted with C57 bone marrow cells (AR epithelium and AR() thymocytes) showed thymus enlargement and androgen insensitivity. Further more, phenotypic analyses of lymphocytes in mice with AR(-) thymic epitheli um showed abrogation of the normal responses to androgens. These data sugge st that AR expressed by thymic epithelium are important modulators of thymo cyte development.