PARADOXICAL NATURE OF MINERALOCORTICOID RECEPTOR ANTAGONISM BY PROGESTINS

Progesterone, but not the synthetic progestagen R-5020, was as good as aldosterone in displacing the mineralocorticoid from its specific receptor in rat kidney both in classical competition studies and in aldosterone binding to MR1 and MR2 components of MR during physical separation. Paradoxically, at equimolar (10-8 M) concentrations, both gestagens (progesterone = 1, R-5020 = 20) were preferentially bound to the MR4 component which coeluted with serum bound 14C-corticosterone (or 14C-progesterone), which could not be labelled with aldosterone in the kidney, and which could not be detected in the liver and the serum under any condition. The MR1 entity, at 10-8 M, was saturated as: aldosterone = 2, R-5020 = 1 = progesterone. Thus, the agonist and the antagonist function in mineralocorticoid action may be expressed by two or more distinct and different sites. © 1979.