Both endogenous and exogenous testosterone decrease myocardial STAT3 activation and SOCS3 expression after acute ischemia and reperfusion

Meijing Wang, Yue Wang, Aaron Abarbanell, Jiangjing Tan, Brent Weil, Jeremy Herrmann, Daniel R. Meldrum

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Background: Signal transducer and activator of transduction 3 (STAT3) pathway has been shown to be cardioprotective. We observed decreased STAT3/suppressor of cytokine signaling 3 (SOCS3) in male hearts, which was associated with worse postischemic myocardial function compared with females. However, it is unclear whether this downregulation of myocardial STAT3/SOCS3 is due to testosterone in males. We hypothesized that after ischemia/reperfusion (I/R), (1) endogenous testosterone decreases myocardial STAT3 and SOCS3 in males, and (2) administration of exogenous testosterone reduces myocardial STAT3/SOCS3 in female and castrated male hearts. Methods: To study this, hearts from I/R injury (Langendorff) were homogenized and assessed for phosphorylated-STAT3 (p-STAT3), total-STAT3 (T-STAT3), SOCS3, and GAPDH by Western blot. We grouped age-matched adult males, females, castrated males, males with androgen receptor blocker-flutamide implantation, females, and castrated males with chronic (3-week) 5α-dihydrotestosterone (DHT) release pellet implantation or acute (5-minute) testosterone infusion (ATI) before ischemia (n = 5-9 per group). Results: Castration or flutamide treatment significantly increased SOCS3 expression in male hearts after I/R. However, only castration increased myocardial STAT3 activation. Notably, DHT replacement or ATI decreased markedly myocardial STAT3/SOCS3 in castrated males and females subjected to I/R. Conclusion: These results suggest that endogenous and exogenous testosterone decrease myocardial STAT3 activation and SOCS3 expression after I/R. This represents the initial demonstration of testosterone-downregulated STAT3/SOCS3 signaling in myocardium.

Original languageEnglish (US)
Pages (from-to)138-144
Number of pages7
JournalSurgery
Volume146
Issue number2
DOIs
StatePublished - Aug 1 2009

ASJC Scopus subject areas

  • Surgery

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