Metabolic derivatives of aldosterone.

Metabolism of aldosterone during the latent period prior to the action of the hormone may be of physiological importance. In the rat, liver metabolizes aldosterone in a sex-dependent manner; larger quantities of neutral polar and reduced aldosterone derivatives are found in male rat kidney; correlating with the larger physiological responses of male rats to aldosterone. The target tissues, mammalian kidney and toad urinary bladder, are also capable of metabolizing aldosterone in situ to neutral polar, 5 alpha- and 5 beta-reduced, and monosulfate derivatives. The 5 alpha-reduced metabolites possess significant antinatriuretic activity and are preferentially synthesized by rat kidney nuclei. The metabolic pathways leading to the synthesis of 5 alpha-reduced metabolites and their subsequent neutral polar derivatives appear to be regulated by dietary sodium and can be inhibited by antimineralocorticoids. At concentrations somewhat higher than aldosterone, these 5 alpha-reduced metabolites also can recreate the development of hypertension and suppress plasma renin activity in young adrenalectomized spontaneously hypertensive rats. Thus, several of the metabolically transformed aldosterone derivatives can be correlated with physiological regulation and/or expression of the actions of the hormone.