This Article  • References  • Full text PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

Critical Role of Testosterone

Matthias W. Wichmann, MD; René Zellweger, MD; Catherine M. DeMaso, MS; Alfred Ayala, PhD; Irshad H. Chaudry, PhD

Arch Surg. 1996;131(11):1186-1192.

Abstract
Objective
To determine whether male sex steroids contribute to the depression in cell-mediated immunity following trauma-hemorrhage and resuscitation.

Design
Two weeks before the induction of soft-tissue trauma (2.5-cm midline laparotomy) and hemorrhagic shock (mean [±SEM] blood pressure, 35±5 mm Hg), male C3H/HeN mice were castrated or sham castrated. Following trauma-hemorrhage, the mice were resuscitated and killed 24 hours thereafter to obtain whole blood and the spleen.

Results
Splenocyte proliferation and splenocyte interleukin-2 and interleukin-3 release were significantly depressed in sham-castrated animals after trauma-hemorrhage. In contrast, these variables in castrated mice after trauma-hemorrhage were similar to those in shamoperated animals. Corticosterone plasma levels were significantly elevated in both trauma-hemorrhage groups compared with those in sham-operated mice. Plasma testosterone levels were undetectable in castrated animals and detectable in sham-castrated mice.

Conclusions
Castration before soft-tissue trauma and hemorrhagic shock maintains normal immune function in male mice, but sham-castrated male mice show significant immunodepression. The maintenance of immune function by androgen deficiency does not seem to be related to changes in the release of corticosterone. We conclude that male sex steroids are involved in the immunodepression observed after trauma-hemorrhage. Thus, the use of testosterone-blocking agents following trauma-hemorrhage should prevent the depression of immune functions and decrease the susceptibility to sepsis under those conditions.

Arch Surg. 1996;131:1186-1192

Author Affiliations
From the Shock and Trauma Research Laboratories, Departments of Surgery (Drs Wichmann, Zellweger, Ayala, and Chaudry and Ms DeMaso), Microbiology (Dr Ayala), and Physiology (Dr Chaudry), Michigan State University, East Lansing; and the Center for Surgical Research, Brown University School of Medicine and Rhode Island Hospital, Providence (Drs Wichmann, Ayala, and Chaudry).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Sex Dimorphism in Wound Healing: The Roles of Sex Steroids and Macrophage Migration Inhibitory Factor
Gilliver et al.
Endocrinology 2008;149:5747-5757.
ABSTRACT | FULL TEXT  

Sex Steroids/Receptor Antagonist: Their Use as Adjuncts After Trauma-Hemorrhage for Improving Immune/Cardiovascular Responses and for Decreasing Mortality from Subsequent Sepsis
Raju and Chaudry
Anesth. Analg. 2008;107:159-166.
ABSTRACT | FULL TEXT  

Gender dimorphism following injury: making the connection from bench to bedside
Sperry and Minei
J. Leukoc. Biol. 2008;83:499-506.
ABSTRACT | FULL TEXT  

Testosterone Reduces Macrophage Expression in the Mouse of Toll-Like Receptor 4, a Trigger for Inflammation and Innate Immunity
Rettew et al.
Biol. Reprod. 2008;78:432-437.
ABSTRACT | FULL TEXT  

Salutary effects of estrogen receptor-beta agonist on lung injury after trauma-hemorrhage
Yu et al.
Am. J. Physiol. Lung Cell. Mol. Physiol. 2006;290:L1004-L1009.
ABSTRACT | FULL TEXT  

Augmentation of T Cell Levels and Responses Induced by Androgen Deprivation
Roden et al.
J. Immunol. 2004;173:6098-6108.
ABSTRACT | FULL TEXT  

Identification of Testosterone-Regulated Genes in Testes of Hypogonadal Mice Using Oligonucleotide Microarray
Sadate-Ngatchou et al.
Mol. Endocrinol. 2004;18:422-433.
ABSTRACT | FULL TEXT  

Androgen-mediated modulation of macrophage function after trauma-hemorrhage: central role of 5{alpha}-dihydrotestosterone
Schneider et al.
J. Appl. Physiol. 2003;95:104-112.
ABSTRACT | FULL TEXT  

The Epidemiology of Severe Sepsis in Children in the United States
Watson et al.
Am. J. Respir. Crit. Care Med. 2003;167:695-701.
ABSTRACT | FULL TEXT  

Estrogen restores cellular immunity in injured male mice via suppression of interleukin-6 production
Messingham et al.
J. Leukoc. Biol. 2001;70:887-895.
ABSTRACT | FULL TEXT  

Attenuation of Vascular Endothelial Dysfunction by Testosterone Receptor Blockade After Trauma and Hemorrhagic Shock
Ba et al.
Arch Surg 2001;136:1158-1163.
ABSTRACT | FULL TEXT  

Divergent Immune Responses in Male and Female Mice after Trauma-Hemorrhage: Dimorphic Alterations in T Lymphocyte Steroidogenic Enzyme Activities
Samy et al.
Endocrinology 2001;142:3519-3529.
ABSTRACT | FULL TEXT  

Testosterone receptor blockade after trauma and hemorrhage attenuates depressed adrenal function
Ba et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000;279:R1841-R1848.
ABSTRACT | FULL TEXT  

Male gender predisposes to development of endotoxic shock in the rat
Losonczy et al.
Cardiovasc Res 2000;47:183-191.
ABSTRACT | FULL TEXT  

Mechanisms of the Salutary Effects of Dehydroepiandrosterone After Trauma-Hemorrhage: Direct or Indirect Effects on Cardiac and Hepatocellular Functions?
Jarrar et al.
Arch Surg 2000;135:416-423.
ABSTRACT | FULL TEXT  

Reversal of sexual dimorphism in splenic T lymphocyte responses after trauma-hemorrhage with aging
Kahlke et al.
Am. J. Physiol. Cell Physiol. 2000;278:C509-C516.
ABSTRACT | FULL TEXT  

Metoclopramide: a novel adjunct for improving cardiac and hepatocellular functions after trauma-hemorrhage
Jarrar et al.
Am. J. Physiol. Endocrinol. Metab. 2000;278:E90-E95.
ABSTRACT | FULL TEXT  

Gender-Based Differences in Outcome in Patients With Sepsis
Eachempati et al.
Arch Surg 1999;134:1342-1347.
ABSTRACT | FULL TEXT  

Male Gender Is a Risk Factor for Major Infections After Surgery
Offner et al.
Arch Surg 1999;134:935-940.
ABSTRACT | FULL TEXT  

Gender Differences in Human Sepsis
Schroder et al.
Arch Surg 1998;133:1200-1205.
ABSTRACT | FULL TEXT  

Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males
Remmers et al.
Am. J. Physiol. Heart Circ. Physiol. 1997;273:H2919-H2925.
ABSTRACT | FULL TEXT  

Testosterone Receptor Blockade After Hemorrhage in Males: Restoration of the Depressed Immune Functions and Improved Survival Following Subsequent Sepsis
Angele et al.
Arch Surg 1997;132:1207-1214.
ABSTRACT  

Male sex steroids are responsible for depressing macrophage immune function after trauma-hemorrhage
Wichmann et al.
Am. J. Physiol. Cell Physiol. 1997;273:C1335-C1340.
ABSTRACT | FULL TEXT  

Decreased 5alpha -dihydrotestosterone catabolism suppresses T lymphocyte functions in males after trauma-hemorrhage
Zheng et al.
Am. J. Physiol. Cell Physiol. 2002;282:C1332-C1338.
ABSTRACT | FULL TEXT