Inhibition of the Sodium-Retaining Influence of Aldosterone by Progesterone*†

Progesterone in a dosage of 50 mg. per day elicited a pronounced natriuretic response in a, woman with Addison’s disease who was treated with aldosterone and cortisone. After the aldosterone had been discontinued, the same amount of progesterone had no influence on urinary sodium excretion. In acute studies performed in 2 other adrenal-deficient subjects, 150 mg. of progesterone nullified the sodium-retaining effect of a slow intravenous infusion of 20 micrograms of aldosterone. Under the same circumstances, progesterone alone had no influence on urinary sodium excretion. The same quantity of progesterone failed to block the effect of 40 or 50 micrograms of aldosterone. These results were interpreted as demonstrating that progesterone is an antagonist of aldosterone, presumably at the level of the renal tubules. It was accordingly assumed that the natriuretic influence of progesterone in normal subjects is due to the inhibition of endogenous aldosterone. In any consideration of the control of sodium metabolism during pregnancy and the luteal phase of the menstrual cycle, this competitive interaction of progesterone and aldosterone must be given a major role.