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

Abstract

The ability of progesterone to increase Na excretion only in the presence of active mineralocorticoids led to the suggestion that progesterone antagonizes mineralocorticoid action at the renal tubular level. The effects of progesterone and aldosterone on Na and K excretion were examined in adrenalectomized rats and these results were compared 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 Na to K ratio with a near maximum effect produced by 1 .mu.g aldosterone. Progesterone alone in doses of 10, 100, and 1000 .mu.g had no significant effect on the Na to K ratio, but when administered simultaneously with 1 .mu.g 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 .mu.g aldosterone. Scatchard analysis of [3H]aldosterone binding to renal receptors in vitro in the presence of progesterone indicated that progesterone inhibited the binding of [3H]aldosterone to both mineralocorticoid and glucocorticoid recpetors. Progesterone was .apprx. 25% as active as aldosterone in inhibiting the formation of [3H]aldosterone complexes with renal cytoplasmic receptors and produced proportional decreases in the binding of [3H]aldosterone to Tris-extractable nuclear receptors and KCl-extractable chromatin-bound 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.