DHEA prevents mineralo- and glucocorticoid receptor-induced chronotropic and hypertrophic actions in isolated rat cardiomyocytes

Article Article scientifique Article DHEA prevents mineralo- and glucocorticoid receptor-induced chronotropic and hypertrophic actions in isolated rat cardiomyocytes eng 2013 author Mannic Tiphaine 738394 author Mouffok Rudman Mounira 604293 author Python Magaly 663290 author Yoshida Takehisa 739657 author Maturana Andres D author Vuilleumier Nicolas 61406 author Rossier Michel 22435 1271-1281 10.1210/en.2012-1784 23397034 0013-7227 Corticosteroids have been involved in the genesis of ventricular arrhythmias associated with pathological heart hypertrophy, although molecular mechanisms responsible for these effects have not been completely explained. Because mineralocorticoid receptor (MR) antagonists have been demonstrated to be beneficial on the cardiac function, much attention has been given to the action of aldosterone on the heart. However, we have previously shown that both aldosterone and corticosterone in vitro induce a marked acceleration of the spontaneous contractions, as well as a significant cell hypertrophy in isolated neonate rat ventricular cardiomyocytes. Moreover, a beneficial role of the steroid hormone dehydroepiandrosterone (DHEA) has been also proposed, but the mechanism of its putative cardioprotective function is not known. We found that DHEA reduces both the chronotropic and the hypertrophic responses of cardiomyocytes upon stimulation of MR and glucocorticoid receptor (GR) in vitro. DHEA inhibitory effects were accompanied by a decrease of T-type calcium channel expression and activity, as assessed by quantitative PCR and the patch-clamp technique. Prevention of cell hypertrophy by DHEA was also revealed by measuring the expression of A-type natriuretic peptide and BNP. The kinetics of the negative chronotropic effect of DHEA, and its sensitivity to actinomycin D, pointed out the presence of both genomic and nongenomic mechanisms of action. Although the genomic action of DHEA was effective mostly upon MR activation, its rapid, nongenomic response appeared related to DHEA antioxidant properties. On the whole, these results suggest new mechanisms for a putative cardioprotective role of DHEA in corticosteroid-associated heart diseases. Aldosterone/pharmacology Animals Antioxidants/pharmacology Calcium Channels, T-Type/genetics/metabolism Cardiotonic Agents/pharmacology Cell Enlargement/drug effects Cells, Cultured Dehydroepiandrosterone/pharmacology Gene Expression/drug effects Heart Rate/drug effects Myocytes, Cardiac/cytology/drug effects/physiology Rats Receptors, Glucocorticoid/metabolism Receptors, Mineralocorticoid/metabolism Dewey 576 136 Département de biologie structurale et bioinformatique 21E false 211 Auto-immunité, inflammation et athérosclérose 270 Endocrinology 154 3 fbb1bce7-bc7d-486c-ba77-d9a1beca206a Article (Published version) Restricted en.2012-1784.pdf 1319597 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de biologie structurale et bioinformatique

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DHEA prevents mineralo- and glucocorticoid receptor-induced chronotropic and hypertrophic actions in isolated rat cardiomyocytes	Endocrinology			2013	548	0

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Yoshida, Takehisa