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

Academic Article

Abstract

  • 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.
  • Authors

    Keywords

  • 17-Hydroxysteroid Dehydrogenases, 3-Hydroxysteroid Dehydrogenases, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Alcohol Oxidoreductases, Animals, Castration, Cell Line, Dihydrotestosterone, Disease Models, Animal, Hemorrhage, Immune Tolerance, Interleukin-2, Interleukin-6, Male, Mice, Mice, Inbred C3H, Sex Factors, T-Lymphocytes, Wounds and Injuries
  • Digital Object Identifier (doi)

    Author List

  • Zheng R; Samy TSA; Schneider CP; Rue LW; Bland KI; Chaudry IH
  • Start Page

  • C1332
  • End Page

  • C1338
  • Volume

  • 282
  • Issue

  • 6