Brief exposure to exogenous testosterone increases death signaling and adversely affects myocardial function after ischemia

Paul R. Crisostomo, Meijing Wang, George M. Wairiuko, Eric D. Morrell, Daniel R. Meldrum

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Chronic endogenous testosterone exposure adversely affects proinflammatory and proapoptotic signaling after ischemia/reperfusion; however, it remains unknown whether a single acute testosterone exposure is equally detrimental. We hypothesized that acute exogenous testosterone infusion before ischemia would worsen myocardial functional recovery, increase the activation of MAPKs and caspase-3, and increase myocardial proinflammatory cytokine production. To study this, isolated-perfused rat hearts (Langendorff) from adult females and castrated males were subjected to 25-min ischemia and 40-min reperfusion with and without acute testosterone infusion (17β-hydroxy-4-androstenone, 10 ng·ml-1·min-1) before ischemia. Myocardial contractile function was continuously recorded. After ischemia/reperfusion, hearts were assessed for levels of testosterone (ELISA), expression of proinflammatory cytokines (ELISA), and activation of MAPKs and caspase-3 (Western blot analysis). Data were analyzed with two-way ANOVA or Student's t-test; P <0.05 was statistically significant. All indices of postischemic functional recovery were decreased with acute exogenous testosterone compared with the untreated groups. Acute testosterone infusion increased activation of MAPKs and caspase-3 following ischemia/ reperfusion. However, there were no significant differences in the myocardial proinflammatory cytokine production after brief testosterone infusion. A single acute exposure to exogenous testosterone before ischemia worsens myocardial functional recovery and increases activation of MAPKs and caspase-3. These findings confirm the deleterious effects of testosterone on myocardium, elucidate the nongenomic mechanistic pathways of testosterone, and may have important clinical implications for patients who have acute exposure to exogenous testosterone.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume290
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

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Testosterone
Ischemia
Caspase 3
Reperfusion
Cytokines
Enzyme-Linked Immunosorbent Assay
Myocardial Ischemia
Myocardium
Analysis of Variance
Western Blotting
Students

Keywords

  • Inflammation
  • Myocardial infarction
  • Sex hormones

ASJC Scopus subject areas

  • Physiology

Cite this

Brief exposure to exogenous testosterone increases death signaling and adversely affects myocardial function after ischemia. / Crisostomo, Paul R.; Wang, Meijing; Wairiuko, George M.; Morrell, Eric D.; Meldrum, Daniel R.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 290, No. 5, 05.2006.

Research output: Contribution to journalArticle

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