Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-9-16
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
623-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Inhibition of 11beta-hydroxysteroid dehydrogenase by bile acids in rats with cirrhosis.
pubmed:affiliation
Division of Nephrology, Departments of Medicine and Clinical Research, University of Berne, Berne, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't