Getting to the heart of glucocorticoid regeneration: 11β-HSD1 and the myocardium

Gillian A Gray; Christopher I White; Raphael Fp Castellan; Sara J McSweeney; Karen  Chapman

doi:10.1530/JME-16-0128

Getting to the heart of glucocorticoid regeneration: 11β-HSD1 and the myocardium

G Gray, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom of Great Britain and Northern Ireland
C White, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom of Great Britain and Northern Ireland
R Castellan, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom of Great Britain and Northern Ireland
S McSweeney, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom of Great Britain and Northern Ireland
K Chapman, Queen\'s Medical Research Institute, University of Ediinburgh, Edinburgh, United Kingdom of Great Britain and Northern Ireland

Correspondence: Gillian Gray, Email: gillian.gray{at}ed.ac.uk

Abstract

Corticosteroids influence 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 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 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 myocardial growth and physiological function. We also consider the potential of 11β-HSD1 as a therapeutic target to enhance repair following myocardial infarction and to prevent the development of cardiac remodeling and heart failure.