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.
LIU, YAN; HAVINGA, RICK; VAN DER LEIJ, FEIKE R.; BOVERHOF, RENZE; SAUER, PIETER J. J.; KUIPERS, FOLKERT; STELLAARD, FRANS
63(4):375-381, April 2008.
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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 7[alpha]-hydroxylase (Cyp7a1), cholesterol 27-hydroxylase (Cyp27), and in particular sterol 12[alpha]-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.
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