Document Detail

Induction of hepatic 11beta-hydroxysteroid dehydrogenase type 1 in patients with alcoholic liver disease.
MedLine Citation:
PMID:  18031327     Owner:  NLM     Status:  MEDLINE    
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.
Adeeba Ahmed; Sushma Saksena; Mark Sherlock; Simon P Olliff; Elwyn Elias; Paul M Stewart
Related Documents :
20094777 - Association of hla-dr14 with the treatment response in japanese patients with autoimmun...
20837947 - Phase i study of vorinostat in patients with advanced solid tumors and hepatic dysfunct...
9017987 - Recovery of portal blood flow after percutaneous transhepatic biliary drainage in patie...
18339077 - Liver adenomatosis: re-evaluation of aetiology and management.
15749177 - Cardiac troponin i release in acute pulmonary embolism in relation to the duration of s...
18069417 - The mcp-1-2518 (a to g) single nucleotide polymorphism in czech patients with pulmonary...
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    
Department of Endocrinology, Division of Medical Sciences, Queen Elizabeth Hospital, Birmingham, UK.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
11-beta-Hydroxysteroid Dehydrogenase Type 1 / biosynthesis,  genetics
Cortisone / blood
Electrolytes / blood
Enzyme Induction / physiology
Hydrocortisone / blood
Kidney / blood supply
Liver / blood supply
Liver Diseases, Alcoholic / metabolism*
Liver Function Tests
Middle Aged
Polymerase Chain Reaction
RNA, Messenger
Grant Support
066357//Wellcome Trust; G84/6638//Medical Research Council
Reg. No./Substance:
0/Electrolytes; 0/RNA, Messenger; 50-23-7/Hydrocortisone; 53-06-5/Cortisone; EC Dehydrogenase Type 1; EC protein, human

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

Previous Document:  Mental and motor development before and during growth hormone treatment in infants and toddlers with...
Next Document:  Immunohistochemical localization of somatostatin receptor subtypes in benign and malignant adrenal t...