title: Heterogeneity of rat liver parenchyma in cholesterol 7 alpha-hydroxylase and bile acid synthesis.
abstract: Periportal and perivenous hepatocytes were isolated from rat liver by digitonin/collagenase perfusion for investigating the acinar distribution of bile acid synthesis. The specific activity of cholesterol 7 alpha-hydroxylase (EC 1.14.13.17) was 7.9-fold higher in perivenous cells than in periportal hepatocytes. Mass production of bile acids differed 4.4-fold between cultured perivenous and periportal hepatocytes. In contrast, the levels of free cholesterol in homogenates and microsomes derived from both subfractions were similar. Feeding of rats with the bile-acid-sequestering anion-exchange resin colestid resulted in a pronounced stimulation of cholesterol 7 alpha-hydroxylase activity and bile acid mass production, but decreased the perivenous/periportal ratio of both parameters. These results demonstrate that bile acid mass production, but decreased the perivenous hepatocytes, possibly owing to feedback suppression by bile acids from the enterohepatic circulation. Furthermore, the opposite acinar localization of cholesterol and bile acid biosynthesis provides an interesting alternative to current views of the regulation of their metabolic pathways.
authors.affiliation: Physiologisch-Chemisches Institut, Universität Tübingen, Federal Republic of Germany.
authors.forename: B
authors.initials: B
authors.lastname: Ugele
authors.forename: H J
authors.initials: HJ
authors.lastname: Kempen
authors.forename: J M
authors.initials: JM
authors.lastname: Kempen
authors.forename: R
authors.initials: R
authors.lastname: Gebhardt
authors.forename: P
authors.initials: P
authors.lastname: Meijer
authors.forename: H J
authors.initials: HJ
authors.lastname: Burger
authors.forename: H M
authors.initials: HM
authors.lastname: Princen
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D003084:Colestipol / Q000494:pharmacology; D005246:Feedback; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D001647:Bile Acids and Salts; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; D003084:Colestipol