The role of aldosterone in regulating epithelial sodium transport is well established as is the concept of a specific intracellular aldosterone or mineralocorticoid receptor (MR). Specific details on the molecular mechanism of this well-characterized physiology have, however, remained sketchy. Two recently published studies offer important insights into two separate aspects of aldosterone action (Shimkets et al. 1994, Wilson et al. 1995). As in many other areas of biology, naturally occurring mutations have again provided key insights.
The syndrome of apparent mineralocorticoid excess (AME) was first characterized by Ulick et al. in 1979. The condition presents in childhood with hypertension, severe hypokalaemic alkalosis, low plasma renin activity and low circulating levels of aldosterone. Treatment with the MR antagonist spironolactone is effective, paradoxically suggesting mineralocorticoid excess. That this condition could be due to a failure of the metabolism of cortisol to cortisone in aldosterone target tissues, such as the kidney or the