title: Corticosteroids Are Essential for Maintaining Cardiovascular Function in Male Mice.
abstract: Activation of the hypothalamic-pituitary-adrenal axis results in the release of hormones from the adrenal glands, including glucocorticoids and mineralocorticoids. The physiological association between corticosteroids and cardiac disease is becoming increasingly recognized; however, the mechanisms underlying this association are not well understood. To determine the biological effects of corticosteroids on the heart, we investigated the impact of adrenalectomy in C57BL/6 male mice. Animals were adrenalectomized (ADX) at 1 month of age and maintained for 3-6 months after surgery to evaluate the effects of long-term adrenalectomy on cardiac function. Morphological evaluation suggested that ADX mice showed significantly enlarged hearts compared with age-matched intact controls. These changes in morphology correlated with deficits in left ventricular (LV) function and electrocardiogram (ECG) abnormalities in ADX mice. Correlating with these functional defects, gene expression analysis of ADX hearts revealed aberrant expression of a large cohort of genes associated with cardiac hypertrophy and arrhythmia. Combined corticosterone and aldosterone replacement treatment prevented the emergence of cardiac abnormalities in ADX mice, whereas corticosterone replacement prevented the effects of adrenalectomy on LV function but did not block the emergence of ECG alterations. Aldosterone replacement did not preserve the LV function but prevented ECG abnormalities. Together, the data indicate that adrenal glucocorticoids and mineralocorticoids either directly or indirectly have selective effects in the heart and their signaling pathways are essential in maintaining normal cardiac function.
authors.affiliation: Signal Transduction Laboratory (D.C.-T., J.A.C.), Comparative Medicine Branch (P.H.M.), and Cellular and Molecular Pathology Branch (J.F.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892; and McAllister Heart Institute (M.S.W.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514.
authors.forename: Diana
authors.initials: D
authors.lastname: Cruz-Topete
authors.affiliation: Signal Transduction Laboratory (D.C.-T., J.A.C.), Comparative Medicine Branch (P.H.M.), and Cellular and Molecular Pathology Branch (J.F.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892; and McAllister Heart Institute (M.S.W.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514.
authors.forename: Page H
authors.initials: PH
authors.lastname: Myers
authors.affiliation: Signal Transduction Laboratory (D.C.-T., J.A.C.), Comparative Medicine Branch (P.H.M.), and Cellular and Molecular Pathology Branch (J.F.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892; and McAllister Heart Institute (M.S.W.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514.
authors.forename: Julie F
authors.initials: JF
authors.lastname: Foley
authors.affiliation: Signal Transduction Laboratory (D.C.-T., J.A.C.), Comparative Medicine Branch (P.H.M.), and Cellular and Molecular Pathology Branch (J.F.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892; and McAllister Heart Institute (M.S.W.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514.
authors.forename: Monte S
authors.initials: MS
authors.lastname: Willis
authors.affiliation: Signal Transduction Laboratory (D.C.-T., J.A.C.), Comparative Medicine Branch (P.H.M.), and Cellular and Molecular Pathology Branch (J.F.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892; and McAllister Heart Institute (M.S.W.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514.
authors.forename: John A
authors.initials: JA
authors.lastname: Cidlowski
mesh_terms: D000315:Adrenalectomy; D000450:Aldosterone / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000378:metabolism* / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000450:Aldosterone; D003345:Corticosterone; D004837:Epinephrine