SODIUM-RETAINING ACTIVITY OF SOME NATURAL AND SYNTHETIC 21-DEOXYSTEROIDS

The effect of progesterone and six other C21-deoxysteroids on renal so dium retention by male adrenalectomized rats was compared with the eff ect exerted by the natural corticoids aldosterone, 11-deoxycorticoster one, and corticosterone. Steroids were active in the following order: aldosterone > 11,19-oxidoprogesterone > 5 alpha H-3,20-pregnanedione g reater than or equal to 5 beta H-3,20-pregnanedione > progesterone = 1 1-ketoprogesterone > 6,19-oxidoprogesterone = 11-keto-6,19-oxidoproges terone greater than or equal to corticosterone. All C21-deoxysteroids, except 11,19-oxidoprogesterone, exhibited parabolic log dose-response functions, indicating an effect that opposes renal sodium retention a t high doses. 11,19-Oxidoprogesterone and the natural corticoids exhib ited normal, exponential, log dose-response curves. Diverse geometric parameters related to molecular planarity were calculated and their co rrelation with biopharmacological properties was attempted. The best l inear regression was obtained for correlation of the concavity of log dose-reponse parabolas (second-order coefficients) of C21-deoxysteroid s with the C3=O/ring D angle of these molecules. A good linear regress ion could also be obtained for correlation of the affinity of C21-deox ysteroids, except 11,19-oxidoprogesterone, for purified type I mineral ocorticoid receptors with those angles. The latter correlation deterio rated upon incorporation of the affinity data for the three natural co rticoids, due to similar affinities of these hormones for type I miner alocorticoid receptors, but could be restored when the binding data fo r the unpurified, corticosterone-binding globulin-containing stage of the receptors were considered. In vivo binding data followed the same trend as that for unpurified receptors.