Testosterone effect on bone marrow, thymus, and suppressor T cells in the (NZB X NZW)F1 mice: its relevance to autoimmunity.

Abstract

The effect of testosterone on the bone marrow, thy-mic, and splenic cells was studied in (NZB x NZW) x F, (B/W) and other strains of mice. The enzyme 20a-hydroxysteroid dehydrogenase (POaSDH), 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 20aSDH activity (70%) resides in the large (10 to 14-p size) cells whereas the small cells (7-p size) demonstrated low activity. Male mice (B/W, BALB/c and BALB/c nude) responded to castration with a decrease in the marrow POaSDH 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 increases in 2OaSDH activity as well as an increase in the relative number of large cells. In the thymus most of the 20aSDH activity (80 to 90%) was found in the PNA-negative (hydrocortisone resistant) thy-mocytes. Orchidectomy caused hypertrophy of the thy-mus and a decrease in thymocytes 2OaSDH activity to-gether with poor responsiveness to PHA; testosterone implant induced thymus atrophy. However, the residual thymocytes from testosterone-treated mice demon-strated high 2OaSDH 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 testos-terone-treated mice may explain why female mice r e spond better to various antigens and why autoimmune disease is more common in female B/W mice. Various observations suggest that the immune system is influ-enced by sex hormones. Female and castrated male mice produce more antibodies to a variety of antigens than do male mice (1). Women have higher incidence of some autoimmune diseases like lupus (2) and rheumatoid arthritis (3). Mice of the B/W strain develop spontaneous autoimmune disease (4, 5). As in human