Androgen Receptors in Thymic Epithelium Modulate Thymus Size and Thymocyte Development*

Abstract

Castration of normal male rodents results in significant enlargement of the thymus, and androgen replacement reverses these changes. Androgen-resistant testicular feminization (Tfm) mice also show significant thymus enlargement, 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 epithelial cells, both of which have been believed to express AR. In the present study immunohistochemical analysis and hormone binding assays were used to demonstrate the presence of AR in thymic epithelial cells. The physiological significance of this epithelial cell AR expression was defined by further studies performed in vivo using chimeric mice, produced by bone marrow transplantation, in which AR expression was limited to either lymphoid or epithelial components of the thymus. Chimeric C57 mice engrafted with Tfm bone marrow cells (AR(+) epithelium and AR(-) thymocytes) had thymuses of normal size and showed the normal involutional response to androgens, whereas chimeric Tfm mice engrafted with C57 bone marrow cells (AR(-) epithelium and AR(+) thymocytes) showed thymus enlargement and androgen insensitivity. Furthermore, phenotypic analyses of lymphocytes in mice with AR(-) thymic epithelium showed abrogation of the normal responses to androgens. These data suggest that AR expressed by thymic epithelium are important modulators of thymocyte development.

Synergistic Effect Between Ouabain and Glucocorticoids for the Induction of Thymic Atrophy

“…Among these steroids, glucocorticoidinduced thymocyte apoptosis is well established (Nordeen et al 1976;McConkey et al 1989;Petit et al 1995;Mann et al 2000;Wiegers et al 2001). Glucocorticoids are known to play a physiological role during thymocyte selection and thymocyte maturation (Vacchio et al 1998), and a pathological role under stress conditions (Cohen 1992;Olsen et al 2001;Zacharchuk et al 1991).…”

Estrogen turns down “the AIRE”

“…These studies showed that thymic epithelial cells express estrogen receptor (ER) and androgen receptor (AR) and that expression of these hormone receptors in the stromal compartment is required for altering bone marrow-derived T cell subsets in the thymus (5,6). In this issue, Dragin et al confirm that sex hormones indeed act on receptors on thymic stromal cells to impinge upon T cell development within the thymus.…”

“…Early clues that sex hormones may also modulate thymic stromal populations, such as mTECs, came from elegant studies that utilized bone marrow chimeras (5,6). These studies showed that thymic epithelial cells express estrogen receptor (ER) and androgen receptor (AR) and that expression of these hormone receptors in the stromal compartment is required for altering bone marrow-derived T cell subsets in the thymus (5,6).…”

Reaction of Thymic Monoamine-Containing Structures to Experimental Testectomy

“…Presumably, the hormone modifies activity of bone marrow polypotent stem cells, stimulates proliferation and migration of these cells, and promotes their differentiation towards erythropoiesis pathway to the detriment of lymphopoiesis, which probably underlies the immunosuppressive effect of testosterone. Along with glucocorticoid, estrogen, and progesterone receptors, thymocytes express receptors for androgens and neurotransmitters, which confirm close relationship between the immune, nervous, and endocrine systems [6,8,9].…”