The sexually dimorphic nature of normal immune responses and the remarkably higher incidence of autoimmune diseases in females have suggested a role for gonadal steroid hormones as modulators of immune system function. We have investigated the effects of androgens on the development of lymphocytes in the thymus and bone marrow. Expression of the androgen receptor, the ligand-activated transcription factor that mediates hormone actions, has been documented in lymphoid and nonlymphoid cells of thymus and bone marrow, but not in mature peripheral lymphocytes. This expression pattern suggests that the major impact of androgens must be on the developmental maturation of T and B lymphocytes rather than on the mature effector cells. Recent experiments have explored whether developing lymphoid precursors are the direct targets of androgen action or whether supporting cells, such as thymic epithelial cells and bone marrow stromal cells, are required for the receptor-mediated effects of androgens on lymphoid cell development. Bone marrow transplantation techniques using an androgen-resistant mouse strain permit the creation of chimeric mice with androgen receptor-defective lymphoid or epithelial/stromal cellular compartments. Hormonal manipulation experiments in these chimeric animals have suggested that thymic epithelial cells and bone marrow stromal cells are mediators of androgenic effects on immature lymphocytes. The long-range goal of these studies is to understand the basis for the disproportionate occurrence of autoimmune diseases in females.
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