Document Detail


Dexamethasone exposure of neonatal rats modulates biliary lipid secretion and hepatic expression of genes controlling bile acid metabolism in adulthood without interfering with primary bile acid kinetics.
MedLine Citation:
PMID:  18356742     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Literature suggests that glucocorticoid (GC) exposure during early life may have long-term consequences into adult life. GCs are known to influence hepatic bile acid synthesis and their transport within the enterohepatic circulation. This study addresses effects of early postnatal exposure to GC on hepatic expression of key genes in bile acid metabolism and bile acid kinetics in adult rats. Male rats were treated with either dexamethasone (DEX) or saline at days 1-3 d after birth. Liver tissue and blood were collected from 2 d to 50 wk of age. Bile acid kinetics were determined at week 8. DEX acutely induced hepatic mRNA levels of cholesterol 7alpha-hydroxylase (Cyp7a1), cholesterol 27-hydroxylase (Cyp27), and in particular sterol 12alpha-hydroxylase (Cyp8b1), whereas expression of the bile acid transporters bile salt export pump (Bsep) and sodium taurocholate cotransporting polypeptide (Ntcp) was moderately affected. Neonatal DEX administration led to increased bilary lipid secretion, decreased Cyp8B1 mRNA expression and a 3-fold higher Cyp7a1/Cyp8b1 mRNA ratio in rats at week 8 compared with age-matched controls without alterations in bile acid kinetics. Therefore, neonatal DEX administration causes altered gene expressions later in life that are not translated into quantitative changes in bile acid kinetics.
Authors:
Yan Liu; Rick Havinga; Feike R VAN DER Leij; Renze Boverhof; Pieter J J Sauer; Folkert Kuipers; Frans Stellaard
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pediatric research     Volume:  63     ISSN:  0031-3998     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-21     Completed Date:  2008-07-03     Revised Date:  2008-08-12    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  375-81     Citation Subset:  IM    
Affiliation:
Center for Liver, Digestive, and Metabolic Disease, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics,  metabolism
Aging / metabolism*
Animals
Animals, Newborn / metabolism*
Bile Acids and Salts / metabolism*
Cholesterol 7-alpha-Hydroxylase / genetics,  metabolism
Cholic Acid / metabolism
Cytochrome P-450 CYP27A1 / genetics,  metabolism
Dexamethasone / pharmacology*
Female
Gene Expression Regulation, Enzymologic / drug effects
Glucocorticoids / pharmacology*
Lipids / secretion*
Liver / enzymology*
Male
Organic Anion Transporters, Sodium-Dependent / genetics,  metabolism
Pregnancy
RNA, Messenger / metabolism
Rats
Steroid 12-alpha-Hydroxylase / genetics,  metabolism
Symporters / genetics,  metabolism
Chemical
Reg. No./Substance:
0/ATP-Binding Cassette Transporters; 0/Abcb11 protein, rat; 0/Bile Acids and Salts; 0/Glucocorticoids; 0/Lipids; 0/Organic Anion Transporters, Sodium-Dependent; 0/RNA, Messenger; 0/Symporters; 145420-23-1/sodium-bile acid cotransporter; 50-02-2/Dexamethasone; 81-25-4/Cholic Acid; EC 1.14.-/Cytochrome P-450 CYP27A1; EC 1.14.-/Steroid 12-alpha-Hydroxylase; EC 1.14.13.17/Cholesterol 7-alpha-Hydroxylase

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


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