Bile acids and their amidates inhibit 11β-hydroxysteroid dehydrogenase obtained from rat kidney

✍ Scribed by F. H. Perschel; H. Bühler; K. Hierholzer

• Publisher: Springer
• Year: 1991
• Tongue: English
• Weight: 548 KB
• Volume: 418
• Category: Article
• ISSN: 0031-6768
• DOI: 10.1007/bf00370568

✦ Synopsis

Recently it has been demonstrated that interaction of corticosteroids with extraadrenal target cells can effectively be modulated by metabolic transformation of the steroid hormone. As far as 11-hydroxylated glucocorticoids are concerned 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) is the most important enzyme charged with target cell metabolism. Inhibition of 11 beta-HSD function either by genetically transmitted deficiency or by exogenous enzyme inhibitors causes severe pathophysiological derangements, which result in a syndrome of "apparent mineralocorticoid excess". In the present paper we have tested whether or not endogenous inhibitors of this enzyme system might exist. The effects of the main naturally occurring mono-, di-, and trihydroxylated bile acids in man on 11 beta-HSD have been studied in in vitro experiments. Using rat renal microsomes it could be demonstrated that unconjugated bile acids of all three classes as well as the corresponding glycine and taurine amidates effectively inhibit oxidative as well as reductive activity of 11 beta-HSD, with lithocholic acid and chenodeoxycholic acid being the most potent compounds. It is concluded that bile acids are potent endogenous inhibitors of 11 beta-HSD and, therefore, could participate in abnormalities of cortisol metabolism observed in liver cirrhosis and extrahepatic biliary obstruction and, possibly, after ingestion of bile acids.