title: Glucocorticoid signaling in the heart: A cardiomyocyte perspective.
abstract: Heart failure is one of the leading causes of death in the Western world. Glucocorticoids are primary stress hormones that regulate a vast array of biological processes, and synthetic derivatives of these steroids have been mainstays in the clinic for the last half century. Abnormal levels of glucocorticoids are known to negatively impact the cardiovascular system; however, surprisingly little is known about the direct role of glucocorticoid signaling in the heart. The actions of glucocorticoids are mediated classically by the glucocorticoid receptor (GR). In certain cells, such as cardiomyocytes, glucocorticoid occupancy and activation of the mineralocorticoid receptor (MR) may also contribute to the observed response. Recently, there has been a surge of reports investigating the in vivo function of glucocorticoid signaling in the heart using transgenic mice that specifically target GR or MR in cardiomyocytes. Results from these studies suggest that GR signaling in cardiomyocytes is critical for the normal development and function of the heart. In contrast, MR signaling in cardiomyocytes participates in the development and progression of cardiac disease. In the following review, we discuss these genetic mouse models and the new insights they are providing into the direct role cardiomyocyte glucocorticoid signaling plays in heart physiology and pathophysiology. This article is part of a Special Issue entitled 'Steroid Perspectives'.
authors: Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 TW Alexander Drive, P.O. Box 12233, MD F3-07, Research Triangle Park, North Carolina 27709, USA. Electronic address: oakleyr2@niehs.nih.gov.
authors: Robert H
authors: RH
authors: Oakley
authors: Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 TW Alexander Drive, P.O. Box 12233, MD F3-07, Research Triangle Park, North Carolina 27709, USA. Electronic address: cidlows1@niehs.nih.gov.
authors: John A
authors: JA
authors: Cidlowski
mesh_terms: D000818:Animals; D005938:Glucocorticoids / Q000378:metabolism*; D006321:Heart / Q000254:growth & development / Q000502:physiology* / Q000503:physiopathology; D006331:Heart Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid
keywords: Cardiomyocytes; Glucocorticoid receptor; Glucocorticoids; Mineralocorticoid receptor; Transgenic mice