Expression of key enzymes in bile acid biosynthesis during development: CYP7B1-mediated activities show tissue-specific differences.
The developmental variation of cytochrome P450 (CYP)7A1, CYP7B1, CYP27A1, and 3beta-hydroxy-Delta(5)-C(27)-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 7alpha-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 3beta-hydroxy-Delta(5)-C(27)-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 7alpha-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 3beta-hydroxy-Delta(5)-C(27)-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
Maria
M
Division of Biochemistry, Department of Pharmaceutical Biosciences, University of Uppsala, Box 578, SE-751 23 Uppsala, Sweden. maria.norlin@farmbio.uu.se
D000375:Aging / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072474:Cytochrome P450 Family 7; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D009919:Orchiectomy; D009928:Organ Specificity; D010446:Peptide Fragments / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011375:Progesterone Reductase / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013250:Steroid Hydroxylases / Q000235:genetics*; D013552:Swine; D014158:Transcription, Genetic
D001647:Bile Acids and Salts; D010446:Peptide Fragments; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D011375:Progesterone Reductase; D013250:Steroid Hydroxylases; C115867:oxysterol 7-alpha-hydroxylase; D000072474:Cytochrome P450 Family 7; C499571:CYP7B1 protein, human