[3H]Aldosterone is transformed into several metabolites by subcellular fractions of rat kidney. 80-90% of the metabolites synthesized by nuclei and plasma membranes are 5 alpha-DHAldo and 3 alpha,5 alpha-THAldo in ratios of 1:2 and 1:1 respectively; small quantities of 3 beta,5 alpha-THAldo are also synthesized. In contrast, kidney cytosol metabolizes Aldo principally to 5 beta-reduced products with co-chromatograph with 5 beta-DHAldo and 3 alpha,5 beta-THAldo. Several polar neutral metabolites, as well as sulfate and acidic metabolites are also synthesized by the cytosol fraction. Similar 5 alpha-reduced metabolites, 5 alpha-DHAldo, 3 alpha,5 alpha-THAldo and 3 beta,5 alpha-THAldo are also synthesized when [3H]aldosterone is incubated in vitro with toad urinary bladder for 1 and 5 h. Significant quantities of 5 beta- and 20 beta-reduced products and sulfate and acidic metabolites are also synthesized. The metabolism of [3H]aldosterone in both target tissues is significantly inhibited by aldosterone antagonists. Several of the reduced metabolites of aldosterone synthesized in kidney and toad bladder possess significant mineralocorticoid activity. 5 alpha-DHAldo and 3 alpha,5 alpha-THAldo possess 1/10 and 1/30 and 3 alpha,5 beta possesses 1/80-1/100 of the antinatriuretic activity of Aldo. It is suggested that the metabolism of Aldo in its target tissues may be linked to regulation or expression of the hormone's actions.
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