INTERACTION OF SYNTHETIC PROGESTAGENS WITH RENAL MINERALOCORTICOID RECEPTORS

Abstract

ABSTRACT Progesterone increases urinary sodium excretion at least in part by competition for renal mineralocorticoid receptors. In contrast, synthetic progestagens do not increase sodium excretion or even cause a slight sodium retention. We therefore compared the ability of progesterone and 12 progesterone like compounds to displace [3H] aldosterone from binding at cytoplasmic mineralocorticoid receptors in rat kidney. All synthetic progesteronelike steroids were less active than progesterone in competing with [3H]aldosterone for the receptor binding: progesterone 100 %, 11β-OH progesterone 50 %, 17 a OH-progesterone 24 % and 16 α-methylprogesterone 3 %. Derivates of 17 α OH-progesterone (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 these compounds.