Antimineralocorticoid Action of Progesterone in the Rat: Correlation of the Effect on Electrolyte Excretion and Interaction with Renal Mineralocorticoid Receptors*

The ability of progesterone to increase sodium excretion only in the presence of active mineralocorticoids has led to the suggestion that progesterone antagonizes mineralocorticoid action at the renal tubular level. We have examined the effects of progesterone and aldosterone on sodium and potassium excretion in adrenalectomized rats and have compared these results with the ability of progesterone to inhibit the binding of aldosterone to cytoplasmic and nuclear mineralocorticoid receptors. The administration of aldosterone to saline-loaded, adrenalectomized male rats resulted in a dose-dependent fall in the urinary sodium to potassium ratio with a near maximum effect produced by 1 μg aldosterone. Progesterone alone in doses of 10, 100, and 1000 μg had no significant effect on the sodium to potassium ratio, but when administered simultaneously with 1 μg aldosterone, the same concentrations of progesterone inhibited the effect of aldosterone in a dose-dependent manner; 1 mg progesterone completely blocked the effect of 1 μg aldosterone. Scatchard analysis of 3Haldosterone binding to renal receptors in vitro in the presence of progesterone indicated that progesterone inhibited the binding of 3Haldosterone to both mineralocorticoid and glucocorticoid receptors. Progesterone was -25% as active as aldosterone in inhibiting the formation of 3Haldosterone complexes with renal cytoplasmic receptors and produced proportional decreases in the binding of 3Haldosterone to Tris-extractable nuclear receptors and KCl-extractable chromatinbound receptors. The comparison of these in vitro receptor studies and in vivo bioassays suggests that progesterone-induced natriuresis results from inhibition of aldosterone binding to renal mineralocorticoid receptors. (Endocrinology102: 1686, 1978)