LAUSR

See related article, pp 189–196 We have come to appreciate the many physiological and pathophysiological functions of adrenal steroid hormones in health and disease and the benefits and adverse effects of therapeutic manipulations. Glucocorticoids are an indispensable component in the treatment of inflammatory conditions. Blockade of the mineralocorticoid receptor (MR) with spironolactone is a long-established diuretic therapy in states of volume overload. In patients with heart failure, MR blockade prolongs survival because of beneficial effects on the heart. In patients with treatment-resistant arterial hypertension, MR blockade has been found to provide superior blood pressure–lowering effects compared with α-blockers and β-blockers.1 Even in patients on hemodialysis, MR blockade seems to prolong survival.2 Much work has been invested in deciphering the molecular pathways involved in steroid hormone function. On ligand binding, steroid hormone receptors translocate to the nucleus to activate or repress target genes. It has been proposed, however, that some of the effects of steroid hormones, including aldosterone, are not mediated by the known MR but rather by nongenomic effects that do not involve gene translation and, therefore, produce a faster response. In contrast to the classical genomic effects, such nongenomic effects are less well understood on a molecular level. In humans, the existence of nongenomic effects has been difficult to prove. Experimental studies suggest that GPR30 may mediate some of the postulated MR-independent effects of aldosterone. Aldosterone-synthase inhibition has been developed as a novel alternative strategy to MR blockade. In contrast to MR blockade, aldosterone-synthase inhibition would be able to attenuate both genomic …