Inhibition of 11beta-hydroxysteroid dehydrogenase by bile acids in rats with cirrhosis

Details

Serval ID
serval:BIB_E300243495AA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Inhibition of 11beta-hydroxysteroid dehydrogenase by bile acids in rats with cirrhosis
Journal
Hepatology
Author(s)
Ackermann  D., Vogt  B., Escher  G., Dick  B., Reichen  J., Frey  B. M., Frey  F. J.
ISSN
0270-9139 (Print)
Publication state
Published
Issued date
09/1999
Volume
30
Number
3
Pages
623-9
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep
Abstract
Renal sodium retention and potassium loss occur early, in many instances in the preascitic state of cirrhosis, an observation that cannot be fully explained by increased aldosterone concentrations. We therefore hypothesize that 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2), which protects mineralocorticoid receptors (MR) from glucocorticosteroids, is down-regulated in cirrhosis. Cirrhosis was induced by bile duct ligation in rats. The urinary ratio of (tetrahydrocorticosterone + 5alpha-tetrahydrocorticosterone)/ 11-dehydro-tetrahydrocorticosterone [(THB+5alpha-THB)/THA] was measured by gas chromatography. Cortical collecting tubules (CCT) were isolated by microdissection and used for measurements of the activity of 11beta-HSD2 by assessing the conversion of corticosterone to dehydrocorticosterone. The mRNA content of 11beta-HSD2 was determined by reverse-transcription polymerase chain reaction (RT-PCR) in CCTs. The urinary ratio of (THB+5alpha-THB)/THA increased concomitantly with the urinary excretion of bile acids following bile duct ligation. Chenodeoxycholic acid (CDCA) dose-dependently inhibited 11beta-HSD2 in CCT with a Ki of 19.9 micromol/L. Four weeks after bile duct ligation, 11beta-HSD2 activity was decreased in CCT, an observation preceded by a reduced mRNA content at weeks 2 and 3. In cirrhosis, the MR-protecting effect by 11beta-HSD2 is diminished, and therefore, endogenous glucocorticoids can induce MR-mediated sodium retention and potassium loss.
Keywords
11-beta-Hydroxysteroid Dehydrogenases Animals Chenodeoxycholic Acid/*pharmacology Corticosterone/urine Hydroxysteroid Dehydrogenases/*antagonists & inhibitors/genetics Kidney Tubules, Collecting/*enzymology Ligation Liver Cirrhosis, Experimental/*enzymology Male Nitric Oxide/physiology RNA, Messenger/analysis Rats Rats, Sprague-Dawley
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 13:03
Last modification date
20/08/2019 16:06
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