Minireview: Aldosterone and Mineralocorticoid Receptors: Past, Present, and Future

Abstract

Although aldosterone was not isolated and chemically characterized until 1953, the mineralocorticoid action of certain steroids, notably deoxycorticosterone (DOC), had been recognized decades earlier. From 1953 until 1990 saw the establishment of the basic biology and clinical (patho)physiology of aldosterone as an epithelial sodium retaining hormone: its biosynthesis in the adrenal glomerulosa; control of its secretion by ACTH, angiotensin II, and plasma [K+]; its action via intracellular mineralocorticoid receptors to promote DNA-directed; RNA-mediated synthesis of proteins responsible for its epithelial effects; and the syndrome of primary aldosteronism, in which secretion of the hormone is relatively autonomous of its normal stimuli. The past 2 decades have been a major extension of our understanding of the pathophysiology of aldosterone and the complexities of mineralocorticoid receptor signaling in particular. This review concludes with a brief consideration of recent findings regarding hormone and receptor, agonists, and antagonists. In 1990 it might reasonably have been argued that we had the overarching framework for understanding the roles of aldosterone and mineralocorticoid receptors, with only the details to be filled in. Two decades later we still do not know the boundaries, and for every answer, two questions are springing up: truly the more we learn, the less we know.