Metabolism of corticosterone in the mouse. Identification of 11 beta, 20 alpha-dihydroxy-3-oxo-4-pregnen-21-oic acid as a major metabolite.

We have shown that mouse liver contains enzymes that catalyze the conversion of the ketol side chain to the 20-hydroxy-21-oic acid side chain. In this paper, we have studied the oxidative metabolism of corticosterone to acidic end products in intact mice. A significant fraction of radioactivity from intraperitoneal injections of [4-14C]corticosterone appeared in liver and intestine within 5 min. The major steroid in liver at 5 min postinjection was found to be corticosterone, although acidic metabolites were detected. Within 30 min after injection, 11 beta, 20 alpha-dihydroxy-3-oxo-preg-4-en-21-oic acid became the dominant steroid. At 60 min, it was the major steroid isolated from liver or intestine. Several other acid metabolites were present in lesser amounts in both organs. About half of the remaining radioactive metabolites in liver and intestine were steroid acids, as determined by their reaction with diazomethane. The identification of the major steroid acid as 11 beta, 20 alpha-dihydroxy-3-oxo-pregn-4-en-21-oic acid was made by comparing the chromatographic behavior of the free acid and its methyl ester with that of authentic synthetic acid using thin layer and high performance liquid chromatography. Identity was confirmed by showing that the specific activities of the homogeneous 14C-labeled free acid remained unchanged when reanalyzed as the 21-methyl ester.