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Am J Physiol Cell Physiol 282: C1332-C1338, 2002. First published February 6, 2002; doi:10.1152/ajpcell.00560.2001
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Vol. 282, Issue 6, C1332-C1338, June 2002

Decreased 5alpha -dihydrotestosterone catabolism suppresses T lymphocyte functions in males after trauma-hemorrhage

Rui Zheng, T. S. Anantha Samy, Christian P. Schneider, Loring W. Rue III, Kirby I. Bland, and Irshad H. Chaudry

Center for Surgical Research and Department of Surgery, University of Alabama School of Medicine, Birmingham, Alabama 35294

Trauma-hemorrhage produces profound immunosuppression in males but not in proestrus females. Prior castration or flutamide treatment of males following trauma-hemorrhage prevents immunosuppression, implicating 5alpha -dihydrotestosterone for the immunosuppressive effects. 5alpha -Dihydrotestosterone, a high-affinity androgen receptor-binding steroid, is synthesized in tissues as needed and seldom accumulates. The presence of steroidogenic enzymes in T lymphocytes suggests both synthesis and catabolism of 5alpha -dihydrotestosterone. We hypothesized, therefore, that the basis for high 5alpha -dihydrotestosterone activity in T lymphocytes of males following trauma-hemorrhage is due to decreased catabolism. Accordingly, catabolism of 5alpha -dihydrotestosterone was assessed in splenic T lymphocytes by examining the activity and expression of enzymes involved. Analysis showed increased synthesis and decreased catabolism of 5alpha -dihydrotestosterone in intact male T lymphocytes following trauma-hemorrhage. In contrast, reduced 5alpha -reductase activity and increased expression of 17beta -hydroxysteroid dehydrogenase oxidative isomers suggest inactivation of 5alpha -dihydrotestosterone in precastrated males. Thus our study suggests increased synthesis and decreased catabolism of 5alpha -dihydrotestosterone as a reason for loss of T lymphocyte functions in intact males following trauma-hemorrhage, as evidenced by decreased release of interleukin-2 and -6.

gonadal steroids; androgen metabolism; cytokines


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