Decreased 5alpha-dihydrotestosterone catabolism suppresses T lymphocyte functions in males after trauma-hemorrhage.
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.
Zheng
Rui
R
Center for Surgical Research and Department of Surgery, University of Alabama School of Medicine, Birmingham, Alabama 35294-0018, USA.
Samy
T S Anantha
TS
Schneider
Christian P
CP
Rue
Loring W
LW
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002369:Castration; D002460:Cell Line; D013196:Dihydrotestosterone / Q000378:metabolism*; D004195:Disease Models, Animal; D006470:Hemorrhage / Q000150:complications / Q000503:physiopathology*; D007108:Immune Tolerance / Q000502:physiology; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012737:Sex Factors; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014947:Wounds and Injuries / Q000150:complications / Q000503:physiopathology*
D007376:Interleukin-2; D015850:Interleukin-6; D013196:Dihydrotestosterone; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D000429:Alcohol Oxidoreductases; C109795:cis-retinol - androgen dehydrogenase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase