Ontogenic development-associated changes in the expression of genes involved in rat bile acid homeostasis.
Ontogenic changes in the rat bile acid (BA) pool, measured enzymatically and by GC-MS, and expression of enzymes (5alpha-reductase, 5beta-reductase, and cytochrome P450 enzymes Cyp7a1, Cyp8b1, Cyp27 and Cyp3a11), transporters [bile salt export pump, sodium taurocholate-cotransporting polypeptide, apical sodium-dependent bile acid transporter, and organic solute transporter alpha/beta (Ostalpha/Ostbeta)], and nuclear receptors [fetoprotein transcription factor (Ftf), farnesoid X receptor (Fxr), small heterodimer partner (Shp), and hepatic nuclear factor 4alpha (HNF-4alpha)], determined by quantitative PCR, were investigated. The absolute size of the 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 in development, in spite of low 5alpha-reductase expression. The relative size of the BA pool, corrected by liver weight, was maintained from 1 week after birth, except at weaning, when a transient peak accompanied by Shp downregulation and Cyp7a1 upregulation 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 the proportion of cholic acid was increased, probably as a result of Cyp8b1 upregulation. In conclusion, changes in the expression of genes involved in BA homeostasis may play a role in physiological adaptations to digestive functions during the rat life span.
Cuesta de Juan
Susana
S
Laboratory of Experimental Hepatology and Drug Targeting, Centro de Investigación Biomédica en Red for Hepatology and Gastroenterology Research (CIBERehd), University of Salamanca, Salamanca, Spain.
Monte
Maria J
MJ
Macias
Rocio I R
RI
Wauthier
Valérie
V
Calderon
Pedro Buc
PB
Marin
Jose J G
JJ
D000367:Age Factors; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000378:metabolism; D019826:Cholic Acid / Q000378:metabolism; D002793:Cholic Acids / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003840:Deoxycholic Acid / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D006706:Homeostasis / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D014886:Weaning; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D019826:Cholic Acid; D002793:Cholic Acids; D003577:Cytochrome P-450 Enzyme System; D004268:DNA-Binding Proteins; D003840:Deoxycholic Acid; D051557:Hepatocyte Nuclear Factor 4; D010088:Oxidoreductases; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C099713:nuclear receptor subfamily 0, group B, member 2; C004821:muricholic acid; C030712:ursocholic acid