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Original Article

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

Paula-Anahi Arias-Loza, Michael C. Kreissl, Susanne Kneitz, Franz R. Kaiser, Ina Israel, Kai Hu, Stefan Frantz, Barbara Bayer, Karl-Heinz Fritzemeier, Kenneth S. Korach, Theo Pelzer
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https://doi.org/10.1161/HYPERTENSIONAHA.111.190389
Hypertension. 2012;HYPERTENSIONAHA.111.190389
Originally published August 14, 2012
Paula-Anahi Arias-Loza
From the Departments of Internal Medicine I (P.-A.A.-L., K.H., S.F., B.B., T.P.) and Nuclear Medicine (M.C.K., F.R.K., I.I.) and Department of Physiological Chemistry I, Biocenter (S.K.), University of Wuerzburg, Wuerzburg, Germany; Bayer HealthCare AG (K.-H.F.), Berlin Germany; Laboratory of Reproductive and Developmental Toxicology NIEHS/NIH (K.S.K.), Research Triangle Park, NC.
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Michael C. Kreissl
From the Departments of Internal Medicine I (P.-A.A.-L., K.H., S.F., B.B., T.P.) and Nuclear Medicine (M.C.K., F.R.K., I.I.) and Department of Physiological Chemistry I, Biocenter (S.K.), University of Wuerzburg, Wuerzburg, Germany; Bayer HealthCare AG (K.-H.F.), Berlin Germany; Laboratory of Reproductive and Developmental Toxicology NIEHS/NIH (K.S.K.), Research Triangle Park, NC.
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Susanne Kneitz
From the Departments of Internal Medicine I (P.-A.A.-L., K.H., S.F., B.B., T.P.) and Nuclear Medicine (M.C.K., F.R.K., I.I.) and Department of Physiological Chemistry I, Biocenter (S.K.), University of Wuerzburg, Wuerzburg, Germany; Bayer HealthCare AG (K.-H.F.), Berlin Germany; Laboratory of Reproductive and Developmental Toxicology NIEHS/NIH (K.S.K.), Research Triangle Park, NC.
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Franz R. Kaiser
From the Departments of Internal Medicine I (P.-A.A.-L., K.H., S.F., B.B., T.P.) and Nuclear Medicine (M.C.K., F.R.K., I.I.) and Department of Physiological Chemistry I, Biocenter (S.K.), University of Wuerzburg, Wuerzburg, Germany; Bayer HealthCare AG (K.-H.F.), Berlin Germany; Laboratory of Reproductive and Developmental Toxicology NIEHS/NIH (K.S.K.), Research Triangle Park, NC.
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Ina Israel
From the Departments of Internal Medicine I (P.-A.A.-L., K.H., S.F., B.B., T.P.) and Nuclear Medicine (M.C.K., F.R.K., I.I.) and Department of Physiological Chemistry I, Biocenter (S.K.), University of Wuerzburg, Wuerzburg, Germany; Bayer HealthCare AG (K.-H.F.), Berlin Germany; Laboratory of Reproductive and Developmental Toxicology NIEHS/NIH (K.S.K.), Research Triangle Park, NC.
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Kai Hu
From the Departments of Internal Medicine I (P.-A.A.-L., K.H., S.F., B.B., T.P.) and Nuclear Medicine (M.C.K., F.R.K., I.I.) and Department of Physiological Chemistry I, Biocenter (S.K.), University of Wuerzburg, Wuerzburg, Germany; Bayer HealthCare AG (K.-H.F.), Berlin Germany; Laboratory of Reproductive and Developmental Toxicology NIEHS/NIH (K.S.K.), Research Triangle Park, NC.
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Stefan Frantz
From the Departments of Internal Medicine I (P.-A.A.-L., K.H., S.F., B.B., T.P.) and Nuclear Medicine (M.C.K., F.R.K., I.I.) and Department of Physiological Chemistry I, Biocenter (S.K.), University of Wuerzburg, Wuerzburg, Germany; Bayer HealthCare AG (K.-H.F.), Berlin Germany; Laboratory of Reproductive and Developmental Toxicology NIEHS/NIH (K.S.K.), Research Triangle Park, NC.
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Barbara Bayer
From the Departments of Internal Medicine I (P.-A.A.-L., K.H., S.F., B.B., T.P.) and Nuclear Medicine (M.C.K., F.R.K., I.I.) and Department of Physiological Chemistry I, Biocenter (S.K.), University of Wuerzburg, Wuerzburg, Germany; Bayer HealthCare AG (K.-H.F.), Berlin Germany; Laboratory of Reproductive and Developmental Toxicology NIEHS/NIH (K.S.K.), Research Triangle Park, NC.
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Karl-Heinz Fritzemeier
From the Departments of Internal Medicine I (P.-A.A.-L., K.H., S.F., B.B., T.P.) and Nuclear Medicine (M.C.K., F.R.K., I.I.) and Department of Physiological Chemistry I, Biocenter (S.K.), University of Wuerzburg, Wuerzburg, Germany; Bayer HealthCare AG (K.-H.F.), Berlin Germany; Laboratory of Reproductive and Developmental Toxicology NIEHS/NIH (K.S.K.), Research Triangle Park, NC.
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Kenneth S. Korach
From the Departments of Internal Medicine I (P.-A.A.-L., K.H., S.F., B.B., T.P.) and Nuclear Medicine (M.C.K., F.R.K., I.I.) and Department of Physiological Chemistry I, Biocenter (S.K.), University of Wuerzburg, Wuerzburg, Germany; Bayer HealthCare AG (K.-H.F.), Berlin Germany; Laboratory of Reproductive and Developmental Toxicology NIEHS/NIH (K.S.K.), Research Triangle Park, NC.
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Theo Pelzer
From the Departments of Internal Medicine I (P.-A.A.-L., K.H., S.F., B.B., T.P.) and Nuclear Medicine (M.C.K., F.R.K., I.I.) and Department of Physiological Chemistry I, Biocenter (S.K.), University of Wuerzburg, Wuerzburg, Germany; Bayer HealthCare AG (K.-H.F.), Berlin Germany; Laboratory of Reproductive and Developmental Toxicology NIEHS/NIH (K.S.K.), Research Triangle Park, NC.
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Abstract

Estrogens attenuate cardiac hypertrophy and increase cardiac contractility via their cognate estrogen receptors (ERs) ERα and ERβ. 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 ERα might be required and sufficient to maintain physiological cardiac glucose uptake in the murine heart. Cardiac glucose uptake quantified in vivo by 18F-fluorodeoxyglucose positron emission tomography was strongly impaired in ovariectomized compared with gonadal intact female C57BL/6JO mice. The selective ERα agonist 16α-LE2 and the nonselective ERα and ERβ agonist 17β-estradiol completely restored cardiac glucose uptake in ovariectomized mice. Cardiac 18F-fluorodeoxyglucose uptake was strongly decreased in female ERα 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 ERα treatment. In conclusion, systemic activation of ERα 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.

  • estrogen receptors
  • cardiac metabolism
  • positron emission tomography
  • glucose transporter
  • hormones
  • Received January 1, 2012.
  • Revision received January 19, 2012.
  • Accepted July 24, 2012.
  • © 2012 American Heart Association, Inc.
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    The Estrogen Receptor-α Is Required and Sufficient to Maintain Physiological Glucose Uptake in the Mouse Heart
    Paula-Anahi Arias-Loza, Michael C. Kreissl, Susanne Kneitz, Franz R. Kaiser, Ina Israel, Kai Hu, Stefan Frantz, Barbara Bayer, Karl-Heinz Fritzemeier, Kenneth S. Korach and Theo Pelzer
    Hypertension. 2012;HYPERTENSIONAHA.111.190389, originally published August 14, 2012
    https://doi.org/10.1161/HYPERTENSIONAHA.111.190389

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    The Estrogen Receptor-α Is Required and Sufficient to Maintain Physiological Glucose Uptake in the Mouse Heart
    Paula-Anahi Arias-Loza, Michael C. Kreissl, Susanne Kneitz, Franz R. Kaiser, Ina Israel, Kai Hu, Stefan Frantz, Barbara Bayer, Karl-Heinz Fritzemeier, Kenneth S. Korach and Theo Pelzer
    Hypertension. 2012;HYPERTENSIONAHA.111.190389, originally published August 14, 2012
    https://doi.org/10.1161/HYPERTENSIONAHA.111.190389
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