50th Anniversary of Aldosterone

This year marks the 50th anniversary of Simpson and Tait’s isolation of electrocortin (aldosterone) (Fig. 1). Five decades of research have yielded extensive insight into the biological actions mediated through this once elusive molecule, in particular, areas of sodium and potassium metabolism and the kidney. The history of discovery surrounding the mechanisms of regulation and action of aldosterone in the 1960s and 1970s provides a unique view of the birth of molecular biology and its consequent impact on the field of genomic research in the 1980s, 1990s, and the 21st century. Interestingly, recent areas of study have focused on the nongenomic effects of aldosterone and its involvement in inflammation and fibrosis in cardiovascular diseases. This has taken what might have at one time been considered a steroid hormone with a narrow pathological consequence into the realm of influencing widely prevalent diseases such as nephropathy, cardiomyopathy, and vasculopathy. Here, we provide a historic review of the discovery of aldosterone, emphasizing its widely expanding involvement in human disease. We begin describing the early years of aldosterone discovery including mention of its involvement in fibrosis by Selye. Next, we explore how molecular biology and genetics yield novel mechanisms of action and regulation. Finally, we revisit the area of nonclassical effects and the expanding involvement of aldosterone in common cardiovascular diseases.