INTERACTION OF SYNTHETIC PROGESTAGENS WITH RENAL MINERALOCORTICOID RECEPTORS

Abstract

Progesterone [P] increases urinary Na excretion at least in part by competition for renal mineralocorticoid receptors. Synthetic progestogens do not increase Na excretion or even cause a slight Na retention. The ability of P and 12 P-like compounds to displace [3H]aldosterone from binding at cytoplasmic mineralocorticoid receptors in rat kidney. All synthetic P-like steroids were less active than P in competing with [3H]aldosterone for the receptor binding: P 100%, 11.beta.-OH[hydroxy]-P 50%, 17-.alpha. OH-P 24% and 16-.alpha.-methyl-P 3%. Derivates of 17-.alpha. OH-P (medrogestone 5%, dydrogestone 4%, medroxy progesterone-acetate 2% and chlormadinone acetate 0.5%) were more potent than 19-nor-testosterone derivates: ethisterone 1%, norethisterone < 1%, norethindrone < 1%, norethylnodrel < 1% and ethynodiol-diacetate < 1%. The decreased affinity of synthetic progestins for mineralocorticoid receptors explains in part the lack of natriuretic activity of the compounds.