Evidence that androgens modulate human thymic T cell output

Background: The thymus has long been recognized as a target for the actions of androgenic hormones, but it has only been recently recognized that alterations in circulating levels of gonadal steroids might affect thymic output of T cells. We had the opportunity to examine parameters of thymic cellular output in several hypogonadal men undergoing androgen replacement therapy. Methods: Circulating naive (CD4⁺CD45RA⁺) T cells were quantitated by flow cytometric analysis of peripheral blood mononuclear cells. Cells bearing T-cell receptor excision circles were quantitated using real-time polymerase chain reaction amplification of DNA isolated from peripheral blood mononuclear cells from healthy men and from hypogonadal men before and after testosterone replacement therapy. Results: CD4⁺CD45⁺ (naive) T cells comprised 10.5% of lymphocytes in healthy males; this proportion was greatly increased in 2 hypogonadal men (35.5% and 44.4%). One man was studied sequentially during treatment with physiologic doses of testosterone. CD4⁺CD45RA⁺ cells fell from 37.36% to 20.05% after 1 month and to 12.51% after 7 months of normalized androgen levels. In 2 hypogonadal patients, T-cell receptor excision circle levels fell by 83% and 78% after androgen replacement therapy. Conclusions: Our observations indicate that the hypogonadal state is associated with increased thymic output of T cells and that this increase in recent thymic emigrants in peripheral blood is reversed by androgen replacement.