Expression of key enzymes in bile acid biosynthesis during development: CYP7B1-mediated activities show tissue-specific differences

Abstract

The developmental variation of cytochrome P450 (CYP)7A1, CYP7B1, CYP27A1, and 3β-hydroxy-Δ⁵-C₂₇-steroid dehydrogenase, key enzymes in bile acid biosynthesis, were investigated in pigs of different ages. As part of these studies, peptide sequences from a purified pig liver oxysterol 7α-hydroxylase were analyzed. The sequences showed a high degree of identity with those of murine and human CYP7B1. Enzymatic activities and mRNA levels of CYP27A1 and 3β-hydroxy-Δ⁵-C₂₇-steroid dehydrogenase were similar in livers of newborn and 6-month-old pigs. Enzymatic activity mediated by CYP7A1 increased several-fold between infancy and adolescence. Hepatic CYP7A1 and CYP7B1 mRNA levels increased several-fold with age. Hepatic microsomal 7α-hydroxylation of 27-hydroxycholesterol and dehydroepiandrosterone, substrates typical for CYP7B1, increased about 5-fold between infancy and adolescence whereas the activities in kidney microsomes decreased at least 10-fold. In conclusion, the results indicate that the expression of CYP27A1 and 3β-hydroxy-Δ⁵-C₂₇-steroid dehydrogenase are similar in livers of newborn and 6-month-old pigs whereas the levels of CYP7A1 increase. The finding that the levels of CYP7B1 increase with age in the liver but decrease in the kidney suggest a tissue-specific developmental regulation of CYP7B1. The age-dependent variation in the liver and kidney suggests that hormonal factors are involved in the regulation of CYP7B1.—Norlin, M. Expression of key enzymes in bile acid biosynthesis during development: CYP7B1-mediated activities show tissue-specific differences. J. Lipid Res. 2002. 43: 721–731.