Aldosterone and its mechanism of action: more questions than answers

The physiology of the steroid hormone, aldosterone is well defined. The molecular events that mediate this response remain to be elucidated. Aldosterone binds to a specific mineralocorticoid receptor (MR) in sodium transporting epithelia. The structural determinants of ligand-binding have been explored through the analysis of steroid resistance syndromes, however, the molecular basis of resistance to aldosterone, pseudo-hypoaldosteronism remains an enigma. Cortisol also binds MR, access is however restricted by the enzyme 11β-hydroxysteroid dehydrogenase. The MR induces specific genes which regulate apical amiloride-sensitive epithelial sodium channels; the finding of activating mutations in Liddles syndrome (pseudoaldosteronism) has emphasised their key role. Such mechanisms may apply not only to the peripheral effects of aldosterone but also to the central regulation of blood pressure.