11-Dehydrocorticosteroids in tissues of mice

Mice were injected with 14 C-corticosterone or 14 C-cortisol, or tissues were incubated with these compounds and extracts were chromatographed on paper. Most radioactivity was recovered as the unchanged steroid and its 11-dehydro metabolite. In vitro formation of 11-dehydrocorticosterone was similar in lung, brain, thymus, spleen, and muscle, while kidney was tenfold greater. The percentage of 11-dehydrocorticosterone found in tissues from injected mice ranged from 1.8 to 13 (average 5.3) in the less active tissues and 41% in kidney. Metabolites formed by kidney were reduced by liver in vitro. In blood the percentage of 11-dehydrocorticosterone after passage through the kidney rose from 1.9 to 5.6, and that of cortisone from 2.0 to 8.2. The values for blood passing through the liver decreased from 7.2 to 4.0 for 11-dehydrocorticosterone and from 6.7 to 2.9 for cortisone. Several 11α-hydroxysteroids injected at a dosage 10 times the 14 C-steroid reduced by half the 11-dehydrocorticosterone or cortisone in kidney, but did not lessen the thymolytic action of cortisone when administered simultaneously. It was concluded that the level of 11-dehydrocorticosteroids found in tissues bears some relationship to the 11β-hydroxysteroid dehydrogenase activity of those tissues and can be lowered by inhibitors of the enzyme. The kidney is a very active site of dehydrogenation, but the liver reduces the metabolites at a comparable rate thereby maintaining the level of active hormone in the general circulation.