Androgen and estrogen receptors in splenic T lymphocytes: Effects of flutamide and trauma-hemorrhage

T. S.Anantha Samy, Martin G. Schwacha, William G. Cioffi, Kirby I. Bland, Irshad H. Chaudry

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

The endogenous sex steroids, testosterone and β-estradiol, play a major role in inflammatory processes. They regulate several cytokine genes by interaction with their intracellular receptors that are, essentially, transcription factors. Because T-lymphocyte functions are altered following trauma-hemorrhage in male mice, we investigated whether (i) receptors for androgen (AR) and estrogen (ER) are present in splenic T lymphocytes, (ii) receptor expressions are altered following trauma-hemorrhage, and (iii) pre-treatment of male mice with the AR antagonist, flutamide, alters receptor expressions and IL-6 release. Analysis of nuclear extracts indicated the presence of AR and ER in splenic T lymphocytes. No difference in receptor expressions between males and females or following trauma-hemorrhage was observed. Pre-treatment of males with flutamide, however, led to increased ER expression in T lymphocytes of sham and trauma-hemorrhaged animals. This suggested that flutamide is capable of inducing the expression of another receptor belonging to a different gonadal steroid. Because response elements for AR and ER are present in the promoter region of the IL-6 gene, release of IL-6 and expression of signal transducer and activator of transcription 3 (STAT3) were analyzed as functional parameters in splenic T lymphocytes. Trauma-hemorrhage decreased IL-6 release by T lymphocytes and the release was restored to sham levels with flutamide pre-treatment. Similarly, STAT3 expression was decreased in T lymphocytes following trauma-hemorrhage and the expression was restored by flutamide pre-treatment. These data collectively demonstrate the importance of gonadal steroids in the regulation of splenic T-lymphocyte functions.

Original languageEnglish (US)
Pages (from-to)465-470
Number of pages6
JournalShock
Volume14
Issue number4
DOIs
StatePublished - Oct 2000
Externally publishedYes

Keywords

  • Androgen antagonist
  • IL-6
  • Immunosuppression
  • STAT 3
  • Sex steroid receptors

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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