The mineralocorticoid receptor (MR) was first characterized 45 years ago (Funder 1972, Rousseau 1972), a decade and a half before its successful cloning (Arriza 1987) to which this issue of the Journal is dedicated. Aldosterone had been isolated and characterized 20 years before the MR: its initial name was electrocortin, reflecting its ability to promote electrolyte transport across epithelial membranes, rapidly changed to its familiar, current name aldosterone. What prompted the change was the finding of a unique aldehyde group at carbon18 of the steroid molecule, the physiological significance of which only became clear many years later (Edwards 1988, Funder 1988).

Not surprisingly, given the rapidly established role of aldosterone in the transepithelial transport of sodium, potassium and water, was that the early running was made by nephrologists and renal physiologists. Although rapid effects of aldosterone on renal sodium transport were reported in early studies (Ganong 1958), later attention focused on the demonstration that aldosterone action could be blocked at the level of DNA transcription (by actinomycin D) or mRNA translation (by puromycin), evidence that aldosterone acted principally at the intracellular level by DNA-directed, RNA-mediated protein synthesis.

This expanded the field of interest beyond the nephrologists to include cell biologists, endocrinologists and clinicians – evidence for the latter are the initial reports of dexamethasone suppressible hyperaldosteronism (Sutherland 1966, New 1967). These were published years before the receptor was characterized by high affinity, displaceable (sometimes bravely termed specific) binding of tritiated aldosterone in kidney slices from adrenalectomized rats; less convincing, in retrospect, was a similar report in rat kidney cytosol (Rousseau 1972), given the subsequent demonstration that molybdate is needed for cytosolic MR to survive in vitro (Emadian 1988).

The interest of endocrinologists was kindled by the recognition that the MR was one of a family …