Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 11
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism
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Aging / metabolism*
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Animals
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Animals, Newborn / metabolism*
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Bile Acids and Salts / metabolism*
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Cholestanetriol 26-Monooxygenase / genetics
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Cholestanetriol 26-Monooxygenase / metabolism
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Cholesterol 7-alpha-Hydroxylase / genetics
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Cholesterol 7-alpha-Hydroxylase / metabolism
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Cholic Acid / metabolism
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Dexamethasone / pharmacology*
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Female
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Gene Expression Regulation, Enzymologic / drug effects
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Glucocorticoids / pharmacology*
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Lipid Metabolism*
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Liver / enzymology*
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Male
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Organic Anion Transporters, Sodium-Dependent / genetics
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Organic Anion Transporters, Sodium-Dependent / metabolism
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Pregnancy
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RNA, Messenger / metabolism
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Rats
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Steroid 12-alpha-Hydroxylase / genetics
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Steroid 12-alpha-Hydroxylase / metabolism
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Symporters / genetics
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Symporters / metabolism
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 11
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ATP-Binding Cassette Transporters
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Abcb11 protein, rat
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Bile Acids and Salts
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Glucocorticoids
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Organic Anion Transporters, Sodium-Dependent
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RNA, Messenger
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Symporters
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sodium-bile acid cotransporter
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Dexamethasone
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Cholesterol 7-alpha-Hydroxylase
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Cholestanetriol 26-Monooxygenase
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Steroid 12-alpha-Hydroxylase
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Cholic Acid