Endocrinology, Vol 136, 1809-1812, Copyright © 1995 by Endocrine Society

ARTICLES

11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta- hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat

GW Souness, SA Latif, JL Laurenzo and DJ Morris
Department of Pathology and Laboratory Medicine, Miriam Hospital, Providence, RI.

The effects of 11 alpha- and 11 beta-hydroxyprogesterone (11 alpha-OHP, 11 beta-OHP), on the activity of the glucocorticoid inactivating enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) were studied. 11 alpha-OHP and 11 beta-OHP were potent inhibitors of both 11 beta-HSD1 in rat liver microsomes and 11 beta-HSD2 in lysates of JEG-3 cells, a human choriocarcinoma cell line. In addition, both progesterone metabolites were markedly potent in conferring mineralocorticoid activity upon B in the adrenalectomized rat. These results provide insight into the structural properties required of inhibitors of 11 beta-HSD activity and indicate a possible role for endogenous 11 beta- HSD inhibitors in the regulation of glucocorticoid-induced Na+ retention.

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