| Role of endogenous testosterone in TNF-induced myocardial injury in males. | |
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MedLine Citation:
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PMID: 22567171 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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BACKGROUND: 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. METHODS: 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. RESULTS: 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, which was associated with higher levels of TNF-induced caspase-8 and caspase-3. Importantly, depletion of endogenous testosterone by castration or blockade of androgen receptor by flutamide treatment abolished TNF-decreased RPP in male hearts. However, castration or flutamide treatment did not affect TNF production and myocardial expression of TNFR1 and TNFR2. CONCLUSION: Our study shows that testosterone is critical to the gender difference in TNF-induced detrimental effects on myocardium. Relative low threshold for TNF-caused myocardial damage in males is likely due to the interaction of testosterone with downstream signals of TNFR1 and/or TNFR2. |
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Authors:
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Meijing Wang; Hongmei Gu; Benjamin D Brewster; Chunyan Huang |
Publication Detail:
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Type: Journal Article Date: 2012-04-08 |
Journal Detail:
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Title: International journal of clinical and experimental medicine Volume: 5 ISSN: 1940-5901 ISO Abbreviation: Int J Clin Exp Med Publication Date: 2012 |
Date Detail:
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Created Date: 2012-05-08 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101471010 Medline TA: Int J Clin Exp Med Country: United States |
Other Details:
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Languages: eng Pagination: 96-104 Citation Subset: - |
Affiliation:
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The Department of Surgery, Indiana University School of Medicine Indianapolis, Indiana. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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