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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/G144    most recent 90515.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Burke, K. T. Articles by Woollett, L. A. PubMed PubMed Citation Articles by Burke, K. T. Articles by Woollett, L. A.

LIVER AND BILIARY TRACT

Hepatic bile acid metabolism in the neonatal hamster: expansion of the bile acid pool parallels increased Cyp7a1 expression levels

Departments of ¹Pathology and Laboratory Medicine, Genome Research Institute, University of Cincinnati Medical School, and ²Mathematical Sciences, University of Cincinnati; and ³Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, General Clinical Research Center, Children's Hospital Medical Center, Cincinnati, Ohio

Submitted 27 August 2008 ; accepted in final form 15 April 2009

Intraluminal concentrations of bile acids are low in newborn infants and increase rapidly after birth, at least partly owing to increased bile acid synthesis rates. The expansion of the bile acid pool is critical since bile acids are required to stimulate bile flow and absorb lipids, a major component of newborn diets. The purpose of the present studies was to determine the mechanism responsible for the increase in bile acid synthesis rates and the subsequent enlargement of bile acid pool sizes (BAPS) during the neonatal period, and how changes in circulating hormone levels might affect BAPS. In the hamster, pool size was low just after birth and increased modestly until 10.5 days postpartum (dpp). BAPS increased more significantly (3-fold) between 10.5 and 15.5 dpp. An increase in mRNA and protein levels of cholesterol 7-hydroxylase (Cyp7a1), the rate-limiting step in classical bile acid synthesis, immediately preceded an increase in BAPS. In contrast, levels of oxysterol 7-hydroxylase (Cyp7b1), a key enzyme in bile acid synthesis by the alternative pathway, were relatively elevated by 1.5 dpp. farnesyl X receptor (FXR) and short heterodimeric partner (SHP) mRNA levels remained relatively constant at a time when Cyp7a1 levels increased. Finally, although simultaneous increases in circulating cortisol and Cyp7a1 levels occurred, precocious expression of Cyp7a1 could not be induced in neonatal hamsters with dexamethasone. Thus the significant increase in Cyp7a1 levels in neonatal hamsters is due to mechanisms independent of the FXR and SHP pathway and cortisol.

neonate; development; FXR; SHP; hormones; FGF15; FGFR4