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

Autor: Mounira Mouffok, Takehisa Yoshida, Andrés D. Maturana, Tiphaine Mannic, Michel F. Rossier, Nicolas Vuilleumier, Magaly Python
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Chronotropic
medicine.medical_specialty
Cardiotonic Agents
medicine.medical_treatment
Gene Expression
Dehydroepiandrosterone
Cardiotonic Agents/pharmacology
Gene Expression/drug effects
Cell Enlargement
Aldosterone/pharmacology
Antioxidants
Muscle hypertrophy
Calcium Channels
T-Type
chemistry.chemical_compound
Receptors
Glucocorticoid
Endocrinology
Mineralocorticoid receptor
Glucocorticoid receptor
Heart Rate
Corticosterone
Receptors
Mineralocorticoid/metabolism
Internal medicine
medicine
polycyclic compounds
Calcium Channels
T-Type/genetics/metabolism
Animals
Myocytes
Cardiac
ddc:576
Aldosterone
Cells
Cultured
Receptors
Glucocorticoid/metabolism
business.industry
Heart Rate/drug effects
Cell Enlargement/drug effects
Rats
Steroid hormone
Dehydroepiandrosterone/pharmacology
Receptors
Mineralocorticoid
chemistry
Antioxidants/pharmacology
Myocytes
Cardiac/cytology/drug effects/physiology
business
hormones
hormone substitutes
and hormone antagonists
Zdroj: Endocrinology, Vol. 154, No 3 (2013) pp. 1271-81
ISSN: 0013-7227
Popis: 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.
Databáze: OpenAIRE
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