The Estrogen Receptor-α Is Required and Sufficient to Maintain Physiological Glucose Uptake in the Mouse Heart

Estrogens attenuate cardiac hypertrophy and increase cardiac contractility via their cognate estrogen receptors (ERs) ER alpha and ER beta. Because female sex hormones enhance global glucose use and because myocardial function and mass are tightly linked to cardiac glucose metabolism, we tested the hypothesis that expression and activation of the ER alpha might be required and sufficient to maintain physiological cardiac glucose uptake in the murine heart. Cardiac glucose uptake quantified in vivo by F-18-fluorodeoxyglucose positron emission tomography was strongly impaired in ovariectomized compared with gonadal intact female C57BL/6JO mice. The selective ER alpha agonist 16 alpha-LE2 and the nonselective ER alpha and ER beta agonist 17 beta-estradiol completely restored cardiac glucose uptake in ovariectomized mice. Cardiac F-18-fluorodeoxyglucose uptake was strongly decreased in female ER alpha knockout mice compared with wild-type littermates. Analysis of cardiac mRNA accumulation by quantitative RT-PCR revealed an upregulation of genes involved in glycolisis and tricarboxylic acid cycle by ER alpha treatment. In conclusion, systemic activation of ER alpha is sufficient, and its expression is required to maintain physiological glucose uptake in the murine heart, which is likely to contribute to known cardioprotective estrogen effects. (Hypertension. 2012; 60: 1070-1077.). Online Data Supplement