Testostrone effect on bone marrow, thymus, and suppressor T cells in the (NZB x NZW)F₁ mice: Its relevance to autoimmunity

The effect of testosterone on the bone marrow, thymic, and splenic cells was studied in (NZB x NZW) x F₁ (B/W) and other strains of mice. The enzyme 20α-hydroxysteroid dehydrogenase (20αSDH), which is found in the T cell lineage, was used as a marker to monitor the effect of testosterone. In the bone marrow most of the 20αSDH activity (70%) resides in the large (10 to 14-μ size) cells whereas the small cells (7-μ size) demonstrated low activity. Male mice (B/W, BALB/c and BALB/c nude) responded to castration with a decrease in the marrow 20αSDH activity concomitantly with a decrease in the number of large marrow cells (and increase in the small cells). Implantation of testosterone into castrated males resulted in a 2-fold increase in 20αSDH activity as well as an increase in the relative number of large cells. In the thymus most of the 20αSDH activity (80 to 90%) was found in the PNA-negative (hydrocortisone resistant) thymocytes. Orchidectomy caused hypertrophy of the thymus and a decrease in thymocytes 20αSDH activity together with poor responsiveness to PHA; testosterone implant induced thymus atrophy. However, the residual thymocytes from testosterone-treated mice demonstrated high 20αSDH activity and good response to PHA. Castration decreased and testosterone replacement therapy increased the activity of splenic suppressor T cells. The enhancement of suppressive activity in testosterone-treated mice may explain why female mice respond better to various antigens and why autoimmune disease is more common in female B/W mice.