Testosterone induces expression of transforming growth factor-beta 1 in the murine thymus

Castration of adult male mice results in enlargement of the thymus and diminution of peripheral suppressor T cell function. Replacement therapy with physiologic doses of androgens reverses these phenomena. Although the mediators involved are unknown, these effects of androgens on the thymus and peripheral immune system are reminiscent of those reported for transforming growth factor-beta (TGF-beta 1). We examined expression of TGF-beta 1 mRNA and bioactive protein in thymuses from castrate and androgen-replaced animals. Steady-state levels of thymic TGF-beta 1 mRNA fell slightly after castration, but rose 2.3-fold after testosterone replacement. Bioactive TGF-beta 1 production by cultured thymic explants also fell following castration to approx. 50% of the levels observed in intact animals. Following 1 week of testosterone replacement in castrate animals, TGF-beta 1 bioactivity produced in culture was restored to levels indistinguishable from those observed with explants from intact animals. Reverse transcription/polymerase chain reaction amplification of RNA revealed that thymocytes are a source of the androgen-modulated TGF-beta 1. These results suggest that TGF-beta 1 may mediate effects of androgens on the immune system.