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.