Transient changes in the expression pattern of key enzymes for bile acid synthesis during rat liver regeneration

Changes in the expression patterns of genes involved in bile acid (BA) synthesis were investigated during rat liver regeneration that follows two-thirds partial hepatectomy. BAs in bile were measured by GC-MS and the absolute and relative abundance of specific mRNAs in the liver by RT-real-time quantitative PCR. Cyclin E mRNA, used as an indicator of liver cell proliferation, peaked at day 1. The levels of mRNA of alpha-fetoprotein transcription factor (FTF) and small heterodimer partner (SHP) were first reduced (day 1) and then (days 2-3) increased, when those of farnesoid X receptor (FXR) were also transiently enhanced. The early (day 1) up-regulation of Cyp7a1, and Cyp8b1, together with the down-regulation of Cyp27, was consistent with an increased proportion of cholic acid versus chenodeoxycholic acid and a progressive recovery in total BAs secretion. The transient appearance of flat BAs (allo-BAs plus Delta4-unsaturated-BAs) during rat liver regeneration was probably due to the changes in the expression ratio of steroid 5alpha- versus 5beta-reductase. Both were first (day 1) down-regulated and then up-regulated (5alpha-reductase more than 5beta-reductase). In conclusion, changes in the expression patterns of nuclear receptors and enzymes involved in BA synthesis are consistent with the transient modifications that occur in BA pool during rat liver regeneration.