PMID: 22567171May 9, 2012Paper

Role of endogenous testosterone in TNF-induced myocardial injury in males.

International Journal of Clinical and Experimental Medicine
Meijing WangChunyan Huang

Abstract

Gender-specific disparities have been observed in myocardium exposed to tumor necrosis factor-α (TNF). Male myocardium demonstrates greater loss in cardiac function in the presence of a given TNF level compared to female. In addition, we have previously demonstrated that estrogen has little influence on reducing TNF-caused myocardial dysfunction in female hearts, suggesting that male hormone - testosterone may be responsible for gender differences in TNF-mediated myocardial damage. Therefore, in this study, we hypothesize that endogenous testosterone plays a detrimental role in TNF-induced myocardial injury in male hearts. Isolated mouse hearts from age-matched adult males, females, castrated males and males treated with androgen receptor blocker-flutamide were subjected to 45 minutes of TNF infusion via a Langendorff model. Left ventricular developed pressure (LVDP) and heart rate were continuously recorded. After TNF infusion, heart tissue was analyzed for myocardial levels of caspase-8 and caspase-3 by Western blot assay. TNF infusion significantly depressed LVDP, but not heart rate in males. Myocardial rate pressure product (RPP, LVDP*heart rate) was markedly decreased in male hearts compared to females in exposure to TNF, ...Continue Reading

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