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A more recent version of this article appeared on June 1, 2007

Papers In Press, published online ahead of print March 1, 2007
J. Lipid Res., doi:10.1194/jlr.M700034-JLR200
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Submitted on January 22, 2007
Revised on March 1, 2007
Accepted on March 1, 2007

Ontogenic development and effect of weaning on the expression of enzymes, transporters and nuclear receptors involved in rat bile acid homeostasis

Susana Cuesta de Juan, Maria J. Monte, Rocio I.R. Macias, Valérie Wauthier, Pedro Buc Calderon, and Jose J.G. Marin

Physiology and Pharmacology, University of Salamanca, Salamanca, Salamanca 37007

Corresponding Author: jjgmarin{at}usal.es

Ontogenic changes in the rat bile acid (BA) pool - measured enzymatically and by GC-MS - and expression of enzymes (Cyp7a1, Cyp8b1, Cyp27, Cyp3a11, 5a-reductase and 5beta -reductase), transporters (Bsep, Ntcp, Asbt and Ostalpha /Ostbeta ) and nuclear receptors (Ftf, Fxr, Shp and Hnf4alpha ) - determined by quantitative PCR were investigated. Absolute size of BA pool increased progressively up to adulthood, whereas the complexity of its composition was high in fetuses, decreased after birth, increased again progressively up to adulthood, and decreased in aged animals. Allo-cholic acid only appeared early on in development, in spite of low 5alpha -reductase expression. The relative size of BA pool, corrected by liver weight, was maintained as from 1 week after birth, except at weaning when a transient peak accompanied by Shp down-regulation and Cyp7a1 up-regulation was observed. An imposed weaning delay of 1 week had no effect on the time-course of the BA pool size but decreased the proportion of chenodeoxycholic and alpha -muricholic acids, whereas that of cholic acid was increased, probably due to Cyp8b1 up-regulation. In conclusion, changes in the expression of genes involved in BA homeostasis may play a role in physiological adaptations to digestive functions during rat life span.


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