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.

Abstract

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.

• Authors: G W Souness, S A Latif, J L Laurenzo, D J Morris
• Journal: Endocrinology (Endocrinology) Vol. 136 Issue 4 Pg. 1809-12 (Apr 1995) ISSN: 0013-7227 [Print] United States
• PMID: 7895695 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Hydroxyprogesterones
• 11-hydroxyprogesterone
• Hydroxysteroid Dehydrogenases
• 11-beta-Hydroxysteroid Dehydrogenases
• Potassium
• Corticosterone

Topics

• 11-beta-Hydroxysteroid Dehydrogenases
• Adrenalectomy
• Animals
• Choriocarcinoma (enzymology)
• Corticosterone (pharmacology)
• Humans
• Hydroxyprogesterones (pharmacology)
• Hydroxysteroid Dehydrogenases (antagonists & inhibitors, metabolism)
• Male
• Microsomes, Liver (enzymology)
• Natriuresis (drug effects)
• Potassium (urine)
• Rats
• Rats, Sprague-Dawley
• Tumor Cells, Cultured