Androgen and estrogen receptors in splenic T lymphocytes: effects of flutamide and trauma-hemorrhage.
The endogenous sex steroids, testosterone and beta-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) pretreatment 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. Pretreatment 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.
Samy
T S
TS
Center for Surgical Research, Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence 02903, USA.
Schwacha
M G
MG
Cioffi
W G
WG
Bland
K I
KI
Chaudry
I H
IH
D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005485:Flutamide / Q000494:pharmacology*; D006470:Hemorrhage / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D012727:Sex Characteristics; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D013739:Testosterone / Q000097:blood; D015534:Trans-Activators / Q000378:metabolism; D014947:Wounds and Injuries / Q000378:metabolism*
D000726:Androgen Antagonists; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D013739:Testosterone; D005485:Flutamide