Document Detail


Induction of hepatic 11beta-hydroxysteroid dehydrogenase type 1 in patients with alcoholic liver disease.
MedLine Citation:
PMID:  18031327     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND AIM: The alcohol-induced pseudo-Cushing's syndrome is an important differential diagnosis of hypercortisolism that is poorly understood. Two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconvert hormonally active cortisol (F) and inactive cortisone (E). Previously we have shown higher urinary F:E metabolite ratios (a reflection of global 11beta-HSD activity) in patients with alcoholic liver disease (ALD) compared to patients with chronic liver disease (CLD) of other aetiologies, suggesting that the phenotype of alcoholic pseudo-Cushing's may relate to altered metabolism of F. SUBJECTS AND METHODS: We performed selective venous sampling of the hepatic, renal and peripheral veins measuring F and E concentrations (using in-house radioimmunoassay) in 20 patients with histologically confirmed ALD and 19 patients with CLD. Six patients who also had selective venous sampling for investigation of suspected hyperaldosteronism were used as 'normal' controls. RESULTS: There was a significant difference in the hepatic F gradient (mean +/- SEM) between groups, indicating increased F production in the liver in patients with ALD (34.5 +/- 21.7 nmol/l) compared to those with CLD (-21.0 +/- 18.5 nmol/l) (P < 0.05) and normals (-19.7 +/- 17.2 nmol/l) (P < 0.05). 11beta-HSD1 mRNA expression was increased fivefold in the ALD group compared with normal controls (P < 0.01). CONCLUSIONS: These results indicate significant induction of HSD11B1 gene expression and activity in patients with ALD during short- and long-term abstinence from alcohol. The mechanism is unknown but might be explained on the basis of alcohol-induced changes in intracellular redox potential or as a protective mechanism to limit liver inflammation and injury. Selective 11beta-HSD1 inhibitors may offer a novel therapeutic approach to treat alcoholic pseudo-Cushing's.
Authors:
Adeeba Ahmed; Sushma Saksena; Mark Sherlock; Simon P Olliff; Elwyn Elias; Paul M Stewart
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-11-19
Journal Detail:
Title:  Clinical endocrinology     Volume:  68     ISSN:  1365-2265     ISO Abbreviation:  Clin. Endocrinol. (Oxf)     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-20     Completed Date:  2009-07-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0346653     Medline TA:  Clin Endocrinol (Oxf)     Country:  England    
Other Details:
Languages:  eng     Pagination:  898-903     Citation Subset:  IM    
Affiliation:
Department of Endocrinology, Division of Medical Sciences, Queen Elizabeth Hospital, Birmingham, UK.
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MeSH Terms
Descriptor/Qualifier:
11-beta-Hydroxysteroid Dehydrogenase Type 1 / biosynthesis,  genetics
Cortisone / blood
Electrolytes / blood
Enzyme Induction / physiology
Female
Humans
Hydrocortisone / blood
Kidney / blood supply
Liver / blood supply
Liver Diseases, Alcoholic / metabolism*
Liver Function Tests
Male
Middle Aged
Polymerase Chain Reaction
RNA, Messenger
Grant Support
ID/Acronym/Agency:
066357//Wellcome Trust; G84/6638//Medical Research Council
Chemical
Reg. No./Substance:
0/Electrolytes; 0/RNA, Messenger; 50-23-7/Hydrocortisone; 53-06-5/Cortisone; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 1; EC 1.1.1.146/HSD11B1 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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