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Getting to the heart of intracellular glucocorticoid regeneration: 11 beta-HSD1 in the myocardium

Gray, GA; White, CI; Castellan, RFP; McSweeney, SJ; Chapman, KE; (2017) Getting to the heart of intracellular glucocorticoid regeneration: 11 beta-HSD1 in the myocardium. Journal of Molecular Endocrinology , 58 (1) R1-R13. 10.1530/JME-16-0128. Green open access

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Abstract

Corticosteroids influence the development and function of the heart and its response to injury and pressure overload via actions on glucocorticoid (GR) and mineralocorticoid (MR) receptors. Systemic corticosteroid concentration depends largely on the activity of the hypothalamic–pituitary–adrenal (HPA) axis, but glucocorticoid can also be regenerated from intrinsically inert metabolites by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), selectively increasing glucocorticoid levels within cells and tissues. Extensive studies have revealed the roles for glucocorticoid regeneration by 11β-HSD1 in liver, adipose, brain and other tissues, but until recently, there has been little focus on the heart. This article reviews the evidence for glucocorticoid metabolism by 11β-HSD1 in the heart and for a role of 11β-HSD1 activity in determining the myocardial growth and physiological function. We also consider the potential of 11β-HSD1 as a therapeutic target to enhance repair after myocardial infarction and to prevent the development of cardiac remodelling and heart failure.

Type: Article
Title: Getting to the heart of intracellular glucocorticoid regeneration: 11 beta-HSD1 in the myocardium
Open access status: An open access version is available from UCL Discovery
DOI: 10.1530/JME-16-0128
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 3.0 Unported License.
Keywords: Endocrinology & Metabolism, 11 beta-HSD1, 11 beta-HSD2, H6PDH, 11 beta-HSD1 inhibitor, cardiomyocyte, fibroblast, macrophage, myocardial infarction, heart failure, 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1, VASCULAR SMOOTH-MUSCLE, MINERALOCORTICOID RECEPTOR, HEXOSE-6-PHOSPHATE DEHYDROGENASE, CARDIAC FIBROBLASTS, CARDIOVASCULAR-DISEASE, INFLAMMATORY RESPONSE, MALE-MICE, MURINE HEART, RAT-HEART
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10042350
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