Immune responses are suppressed in males, but not in proestrous females, after
trauma-
hemorrhage.
Testosterone and 17beta-estradiol appear to be responsible for divergent immune effects. There is considerable evidence to suggest
sex steroid hormone involvement in immune functions. As formation of active
steroid depends on the activity of
androgen- and
estrogen-synthesizing
enzymes, expression and activity of 5alpha-reductase,
aromatase, and 3beta- and 17beta-
hydroxysteroid dehydrogenases were determined in spleen and T lymphocytes of male and proestrous female mice after
trauma-
hemorrhage. All of the
enzymes were present in spleen, specifically in T lymphocytes. 5alpha-Reductase expression and activity increased in male T lymphocytes, whereas
aromatase activity, but not expression, increased in female T lymphocytes. Increased 5alpha-reductase activity in male T lymphocytes is immunosuppressive because of increased 5alpha-dihydrotestosterone synthesis, whereas in females increased
aromatase activity triggering 17beta-estradiol synthesis is immunoprotective. This study also demonstrates the importance of
17beta-hydroxysteroid dehydrogenase oxidative and reductive functions. The immunoprotection of proestrous females is associated with enhanced
reductase function of the
enzyme. In males, decreased expression of oxidative isomer type IV, which impairs catabolism of 5alpha-dihydrotestosterone, probably augments immunosuppression. This study provides evidence for the involvement of intracrine sex
steroid synthesis in gender dimorphic immune responses after
trauma-
hemorrhage.