Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1998 Jan 1;329(Pt 1):17–35. doi: 10.1042/bj3290017

Zonation of hepatic cytochrome P-450 expression and regulation.

T Oinonen 1, K O Lindros 1
PMCID: PMC1219009  PMID: 9405271

Abstract

The CYP genes encode enzymes of the cytochrome P-450 superfamily. Cytochrome P-450 (CYP) enzymes are expressed mainly in the liver and are active in mono-oxygenation and hydroxylation of various xenobiotics, including drugs and alcohols, as well as that of endogenous compounds such as steroids, bile acids, prostaglandins, leukotrienes and biogenic amines. In the liver the CYP enzymes are constitutively expressed and commonly also induced by chemicals in a characteristic zonated pattern with high expression prevailing in the downstream perivenous region. In the present review we summarize recent studies, mainly based on rat liver, on the factors regulating this position-dependent expression and induction. Pituitary-dependent signals mediated by growth hormone and thyroid hormone seem to selectively down-regulate the upstream periportal expression of certain CYP forms. It is at present unknown to what extent other hormones that also affect total hepatic CYP activities, i.e. insulin, glucagon, glucocorticoids and gonadal hormones, act zone-specifically. The expression and induction of CYP enzymes in the perivenous region probably have important toxicological implications, since many CYP-activated chemicals cause cell injury primarily in this region of the liver.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abdel-Razzak Z., Loyer P., Fautrel A., Gautier J. C., Corcos L., Turlin B., Beaune P., Guillouzo A. Cytokines down-regulate expression of major cytochrome P-450 enzymes in adult human hepatocytes in primary culture. Mol Pharmacol. 1993 Oct;44(4):707–715. [PubMed] [Google Scholar]
  2. Aldridge T. C., Tugwood J. D., Green S. Identification and characterization of DNA elements implicated in the regulation of CYP4A1 transcription. Biochem J. 1995 Mar 1;306(Pt 2):473–479. doi: 10.1042/bj3060473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aoyama T., Gonzalez F. J., Gelboin H. V. Mutagen activation by cDNA-expressed P(1)450, P(3)450, and P450a. Mol Carcinog. 1989;1(4):253–259. doi: 10.1002/mc.2940010408. [DOI] [PubMed] [Google Scholar]
  4. Barker C. W., Fagan J. B., Pasco D. S. Down-regulation of P4501A1 and P4501A2 mRNA expression in isolated hepatocytes by oxidative stress. J Biol Chem. 1994 Feb 11;269(6):3985–3990. [PubMed] [Google Scholar]
  5. Barnett C. R., Flatt P. R., Ioannides C. Modulation of the rat hepatic cytochrome P450 composition by long-term streptozotocin-induced insulin-dependent diabetes. J Biochem Toxicol. 1994 Apr;9(2):63–69. doi: 10.1002/jbt.2570090203. [DOI] [PubMed] [Google Scholar]
  6. Baron J., Redick J. A., Guengerich F. P. An immunohistochemical study on the localization and distributions of phenobarbital- and 3-methylcholanthrene-inducible cytochromes P-450 within the livers of untreated rats. J Biol Chem. 1981 Jun 10;256(11):5931–5937. [PubMed] [Google Scholar]
  7. Baron J., Redick J. A., Guengerich F. P. An immunohistochemical study on the localization and distributions of phenobarbital- and 3-methylcholanthrene-inducible cytochromes P-450 within the livers of untreated rats. J Biol Chem. 1981 Jun 10;256(11):5931–5937. [PubMed] [Google Scholar]
  8. Baron J., Redick J. A., Guengerich F. P. Effects of 3-methylcholanthrene, beta-naphthoflavone, and phenobarbital on the 3-methylcholanthrene-inducible isozyme of cytochrome P-450 within centrilobular, midzonal, and periportal hepatocytes. J Biol Chem. 1982 Jan 25;257(2):953–957. [PubMed] [Google Scholar]
  9. Baron J., Redick J. A., Guengerich F. P. Immunohistochemical localizations of cytochromes P-450 in rat liver. Life Sci. 1978 Dec 25;23(26):2627–2632. doi: 10.1016/0024-3205(78)90380-6. [DOI] [PubMed] [Google Scholar]
  10. Baron J., Voigt J. M., Whitter T. B., Kawabata T. T., Knapp S. A., Guengerich F. P., Jakoby W. B. Identification of intratissue sites for xenobiotic activation and detoxication. Adv Exp Med Biol. 1986;197:119–144. doi: 10.1007/978-1-4684-5134-4_10. [DOI] [PubMed] [Google Scholar]
  11. Bars R. G., Bell D. R., Elcombe C. R. Induction of cytochrome P450 and peroxisomal enzymes by clofibric acid in vivo and in vitro. Biochem Pharmacol. 1993 May 25;45(10):2045–2053. doi: 10.1016/0006-2952(93)90015-o. [DOI] [PubMed] [Google Scholar]
  12. Bars R. G., Bell D. R., Elcombe C. R., Oinonen T., Jalava T., Lindros K. O. Zone-specific inducibility of cytochrome P450 2B1/2 is retained in isolated perivenous hepatocytes. Biochem J. 1992 Mar 15;282(Pt 3):635–638. doi: 10.1042/bj2820635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Bars R. G., Elcombe C. R. Dose-dependent acinar induction of cytochromes P450 in rat liver. Evidence for a differential mechanism of induction of P450IA1 by beta-naphthoflavone and dioxin. Biochem J. 1991 Jul 15;277(Pt 2):577–580. doi: 10.1042/bj2770577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Bars R. G., Mitchell A. M., Wolf C. R., Elcombe C. R. Induction of cytochrome P-450 in cultured rat hepatocytes. The heterogeneous localization of specific isoenzymes using immunocytochemistry. Biochem J. 1989 Aug 15;262(1):151–158. doi: 10.1042/bj2620151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Bell D. R., Bars R. G., Gibson G. G., Elcombe C. R. Localization and differential induction of cytochrome P450IVA and acyl-CoA oxidase in rat liver. Biochem J. 1991 Apr 1;275(Pt 1):247–252. doi: 10.1042/bj2750247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Bengtsson G., Julkunen A., Penttilä K. E., Lindros K. O. Effect of phenobarbital on the distribution of drug metabolizing enzymes between periportal and perivenous rat hepatocytes prepared by digitonin-collagenase liver perfusion. J Pharmacol Exp Ther. 1987 Feb;240(2):663–667. [PubMed] [Google Scholar]
  17. Berg A., Gustafsson J. A. Regulation of hydroxylation of 5 alpha-androstane-3 beta, 17 beta-diol in liver microsomes from male and female rats. J Biol Chem. 1973 Sep 25;248(18):6559–6567. [PubMed] [Google Scholar]
  18. Berkowitz C. M., Shen C. S., Bilir B. M., Guibert E., Gumucio J. J. Different hepatocytes express the cholesterol 7 alpha-hydroxylase gene during its circadian modulation in vivo. Hepatology. 1995 Jun;21(6):1658–1667. doi: 10.1016/0270-9139(95)90472-7. [DOI] [PubMed] [Google Scholar]
  19. Bhattacharyya K. K., Brake P. B., Eltom S. E., Otto S. A., Jefcoate C. R. Identification of a rat adrenal cytochrome P450 active in polycyclic hydrocarbon metabolism as rat CYP1B1. Demonstration of a unique tissue-specific pattern of hormonal and aryl hydrocarbon receptor-linked regulation. J Biol Chem. 1995 May 12;270(19):11595–11602. doi: 10.1074/jbc.270.19.11595. [DOI] [PubMed] [Google Scholar]
  20. Botham K. M., Lawson M. E., Beckett G. J., Percy-Robb I. W., Boyd G. S. Portal blood concentrations of conjugated cholic and chenodeoxycholic acids. Relationships to bile salt synthesis in liver cells. Biochim Biophys Acta. 1981 Jul 24;665(1):81–87. doi: 10.1016/0005-2760(81)90235-6. [DOI] [PubMed] [Google Scholar]
  21. Brassil P. J., Edwards R. J., Davies D. S. Expression and distribution of cholesterol 7 alpha-hydroxylase in rat liver. Biochem Pharmacol. 1995 Jul 31;50(3):311–316. doi: 10.1016/0006-2952(95)00144-o. [DOI] [PubMed] [Google Scholar]
  22. Buchmann A., Kunz W., Wolf C. R., Oesch F., Robertson L. W. Polychlorinated biphenyls, classified as either phenobarbital- or 3-methylcholanthrene-type inducers of cytochrome P-450, are both hepatic tumor promoters in diethylnitrosamine-initiated rats. Cancer Lett. 1986 Sep;32(3):243–253. doi: 10.1016/0304-3835(86)90176-x. [DOI] [PubMed] [Google Scholar]
  23. Burger H. J., Schuetz E. G., Schuetz J. D., Guzelian P. S. Divergent effects of cycloheximide on the induction of class II and class III cytochrome P450 mRNAs in cultures of adult rat hepatocytes. Arch Biochem Biophys. 1990 Sep;281(2):204–211. doi: 10.1016/0003-9861(90)90433-y. [DOI] [PubMed] [Google Scholar]
  24. Burger H. J., Schuetz J. D., Schuetz E. G., Guzelian P. S. Paradoxical transcriptional activation of rat liver cytochrome P-450 3A1 by dexamethasone and the antiglucocorticoid pregnenolone 16 alpha-carbonitrile: analysis by transient transfection into primary monolayer cultures of adult rat hepatocytes. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2145–2149. doi: 10.1073/pnas.89.6.2145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Bühler R., Lindros K. O., Nordling A., Johansson I., Ingelman-Sundberg M. Zonation of cytochrome P450 isozyme expression and induction in rat liver. Eur J Biochem. 1992 Feb 15;204(1):407–412. doi: 10.1111/j.1432-1033.1992.tb16650.x. [DOI] [PubMed] [Google Scholar]
  26. Chen L., Davis G. J., Crabb D. W., Lumeng L. Intrasplenic transplantation of isolated periportal and perivenous hepatocytes as a long-term system for study of liver-specific gene expression. Hepatology. 1994 Apr;19(4):989–998. [PubMed] [Google Scholar]
  27. Christou M., Savas U., Schroeder S., Shen X., Thompson T., Gould M. N., Jefcoate C. R. Cytochromes CYP1A1 and CYP1B1 in the rat mammary gland: cell-specific expression and regulation by polycyclic aromatic hydrocarbons and hormones. Mol Cell Endocrinol. 1995 Nov 30;115(1):41–50. doi: 10.1016/0303-7207(95)03668-w. [DOI] [PubMed] [Google Scholar]
  28. Debri K., Boobis A. R., Davies D. S., Edwards R. J. Distribution and induction of CYP3A1 and CYP3A2 in rat liver and extrahepatic tissues. Biochem Pharmacol. 1995 Dec 22;50(12):2047–2056. doi: 10.1016/0006-2952(95)02107-8. [DOI] [PubMed] [Google Scholar]
  29. Denison M. S. Heterogeneity of rat hepatic Ah receptor: identification of two receptor forms which differ in their biochemical properties. J Biochem Toxicol. 1992 Winter;7(4):249–256. doi: 10.1002/jbt.2570070408. [DOI] [PubMed] [Google Scholar]
  30. Denison M. S., Whitlock J. P., Jr Xenobiotic-inducible transcription of cytochrome P450 genes. J Biol Chem. 1995 Aug 4;270(31):18175–18178. doi: 10.1074/jbc.270.31.18175. [DOI] [PubMed] [Google Scholar]
  31. Denison M. S., Yao E. F. Characterization of the interaction of transformed rat hepatic cytosolic Ah receptor with a dioxin responsive transcriptional enhancer. Arch Biochem Biophys. 1991 Jan;284(1):158–166. doi: 10.1016/0003-9861(91)90278-q. [DOI] [PubMed] [Google Scholar]
  32. Dicker E., McHugh T., Cederbaum A. I. Increased catalytic activity of cytochrome P-450IIE1 in pericentral hepatocytes compared to periportal hepatocytes isolated from pyrazole-treated rats. Biochim Biophys Acta. 1991 Mar 4;1073(2):316–323. doi: 10.1016/0304-4165(91)90137-6. [DOI] [PubMed] [Google Scholar]
  33. Eaton D. L., Gallagher E. P., Bammler T. K., Kunze K. L. Role of cytochrome P4501A2 in chemical carcinogenesis: implications for human variability in expression and enzyme activity. Pharmacogenetics. 1995 Oct;5(5):259–274. doi: 10.1097/00008571-199510000-00001. [DOI] [PubMed] [Google Scholar]
  34. Einarsson K., Gustafsson J. A., Stenberg A. Neonatal imprinting of liver microsomal hydroxylation and reduction of steroids. J Biol Chem. 1973 Jul 25;248(14):4987–4997. [PubMed] [Google Scholar]
  35. Ekberg S., Carlsson L., Carlsson B., Billig H., Jansson J. O. Plasma growth hormone pattern regulates epidermal growth factor (EGF) receptor messenger ribonucleic acid levels and EGF binding in the rat liver. Endocrinology. 1989 Oct;125(4):2158–2166. doi: 10.1210/endo-125-4-2158. [DOI] [PubMed] [Google Scholar]
  36. Elferink C. J., Gasiewicz T. A., Whitlock J. P., Jr Protein-DNA interactions at a dioxin-responsive enhancer. Evidence that the transformed Ah receptor is heteromeric. J Biol Chem. 1990 Nov 25;265(33):20708–20712. [PubMed] [Google Scholar]
  37. Elferink C. J., Whitlock J. P., Jr Dioxin-dependent, DNA sequence-specific binding of a multiprotein complex containing the Ah receptor. Receptor. 1994 Fall;4(3):157–173. [PubMed] [Google Scholar]
  38. Eliasson E., Johansson I., Ingelman-Sundberg M. Ligand-dependent maintenance of ethanol-inducible cytochrome P-450 in primary rat hepatocyte cell cultures. Biochem Biophys Res Commun. 1988 Jan 15;150(1):436–443. doi: 10.1016/0006-291x(88)90539-6. [DOI] [PubMed] [Google Scholar]
  39. Favreau L. V., Malchoff D. M., Mole J. E., Schenkman J. B. Responses to insulin by two forms of rat hepatic microsomal cytochrome P-450 that undergo major (RLM6) and minor (RLM5b) elevations in diabetes. J Biol Chem. 1987 Oct 15;262(29):14319–14326. [PubMed] [Google Scholar]
  40. Fernandez-Salguero P., Pineau T., Hilbert D. M., McPhail T., Lee S. S., Kimura S., Nebert D. W., Rudikoff S., Ward J. M., Gonzalez F. J. Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. Science. 1995 May 5;268(5211):722–726. doi: 10.1126/science.7732381. [DOI] [PubMed] [Google Scholar]
  41. Foster J. R., Elcombe C. R., Boobis A. R., Davies D. S., Sesardic D., McQuade J., Robson R. T., Hayward C., Lock E. A. Immunocytochemical localization of cytochrome P-450 in hepatic and extra-hepatic tissues of the rat with a monoclonal antibody against cytochrome P-450 c. Biochem Pharmacol. 1986 Dec 15;35(24):4543–4554. doi: 10.1016/0006-2952(86)90777-x. [DOI] [PubMed] [Google Scholar]
  42. Gaasbeek Janzen J. W., Lamers W. H., Moorman A. F., de Graaf A., Los J. A., Charles R. Immunohistochemical localization of carbamoyl-phosphate synthetase (ammonia) in adult rat liver; evidence for a heterogeneous distribution. J Histochem Cytochem. 1984 Jun;32(6):557–564. doi: 10.1177/32.6.6373912. [DOI] [PubMed] [Google Scholar]
  43. Gascon-Barré M., Benbrahim N., Tremblay C. Hepatic zonation of drug metabolizing enzymes. Studies on hepatocytes isolated from the periportal or perivenous region of the liver acinus. Can J Physiol Pharmacol. 1989 Sep;67(9):1015–1022. doi: 10.1139/y89-160. [DOI] [PubMed] [Google Scholar]
  44. Gasiewicz T. A., Bauman P. A. Heterogeneity of the rat hepatic Ah receptor and evidence for transformation in vitro and in vivo. J Biol Chem. 1987 Feb 15;262(5):2116–2120. [PubMed] [Google Scholar]
  45. Gasiewicz T. A., Rucci G. Alpha-naphthoflavone acts as an antagonist of 2,3,7, 8-tetrachlorodibenzo-p-dioxin by forming an inactive complex with the Ah receptor. Mol Pharmacol. 1991 Nov;40(5):607–612. [PubMed] [Google Scholar]
  46. Gebert C. A., Park S. H., Waxman D. J. Regulation of signal transducer and activator of transcription (STAT) 5b activation by the temporal pattern of growth hormone stimulation. Mol Endocrinol. 1997 Apr;11(4):400–414. doi: 10.1210/mend.11.4.9904. [DOI] [PubMed] [Google Scholar]
  47. Gebhardt R., Alber J., Wegner H., Mecke D. Different drug metabolizing capacities in cultured periportal and pericentral hepatocytes. Biochem Pharmacol. 1994 Aug 17;48(4):761–766. doi: 10.1016/0006-2952(94)90054-x. [DOI] [PubMed] [Google Scholar]
  48. Gebhardt R., Gaunitz F., Mecke D. Heterogeneous (positional) expression of hepatic glutamine synthetase: features, regulation and implications for hepatocarcinogenesis. Adv Enzyme Regul. 1994;34:27–56. doi: 10.1016/0065-2571(94)90007-8. [DOI] [PubMed] [Google Scholar]
  49. Gebhardt R., Mecke D. Heterogeneous distribution of glutamine synthetase among rat liver parenchymal cells in situ and in primary culture. EMBO J. 1983;2(4):567–570. doi: 10.1002/j.1460-2075.1983.tb01464.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Gebhardt R. Metabolic zonation of the liver: regulation and implications for liver function. Pharmacol Ther. 1992;53(3):275–354. doi: 10.1016/0163-7258(92)90055-5. [DOI] [PubMed] [Google Scholar]
  51. Goldstein J. A., Linko P. Differential induction of two 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible forms of cytochrome P-450 in extrahepatic versus hepatic tissues. Mol Pharmacol. 1984 Jan;25(1):185–191. [PubMed] [Google Scholar]
  52. Goldstein J. A., Linko P., Luster M. I., Sundheimer D. W. Purification and characterization of a second form of hepatic cytochrome P-448 from rats treated with a pure polychlorinated biphenyl isomer. J Biol Chem. 1982 Mar 10;257(5):2702–2707. [PubMed] [Google Scholar]
  53. Gonzalez F. J., Liu S. Y., Yano M. Regulation of cytochrome P450 genes: molecular mechanisms. Pharmacogenetics. 1993 Feb;3(1):51–57. doi: 10.1097/00008571-199302000-00006. [DOI] [PubMed] [Google Scholar]
  54. Gonzalez F. J. Molecular genetics of the P-450 superfamily. Pharmacol Ther. 1990;45(1):1–38. doi: 10.1016/0163-7258(90)90006-n. [DOI] [PubMed] [Google Scholar]
  55. Gooding P. E., Chayen J., Sawyer B., Slater T. F. Cytochrome P-450 distribution in rat liver and the effect of sodium phenobarbitone administration. Chem Biol Interact. 1978 Mar;20(3):299–310. doi: 10.1016/0009-2797(78)90108-4. [DOI] [PubMed] [Google Scholar]
  56. Guengerich F. P., Dannan G. A., Wright S. T., Martin M. V., Kaminsky L. S. Purification and characterization of liver microsomal cytochromes p-450: electrophoretic, spectral, catalytic, and immunochemical properties and inducibility of eight isozymes isolated from rats treated with phenobarbital or beta-naphthoflavone. Biochemistry. 1982 Nov 9;21(23):6019–6030. doi: 10.1021/bi00266a045. [DOI] [PubMed] [Google Scholar]
  57. Guengerich F. P. The 1992 Bernard B. Brodie Award Lecture. Bioactivation and detoxication of toxic and carcinogenic chemicals. Drug Metab Dispos. 1993 Jan-Feb;21(1):1–6. [PubMed] [Google Scholar]
  58. Guzelian P. S., Li D., Schuetz E. G., Thomas P., Levin W., Mode A., Gustafsson J. A. Sex change in cytochrome P-450 phenotype by growth hormone treatment of adult rat hepatocytes maintained in a culture system on matrigel. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9783–9787. doi: 10.1073/pnas.85.24.9783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Hassett C., Luchtel D. L., Omiecinski C. J. Hepatic expression of rat P450 mRNA assessed by in situ hybridization to oligomer probes. DNA. 1989 Jan-Feb;8(1):29–37. doi: 10.1089/dna.1.1989.8.29. [DOI] [PubMed] [Google Scholar]
  60. Hellkamp J., Christ B., Bastian H., Jungermann K. Modulation by oxygen of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures. Eur J Biochem. 1991 Jun 15;198(3):635–639. doi: 10.1111/j.1432-1033.1991.tb16061.x. [DOI] [PubMed] [Google Scholar]
  61. Hirvonen A., Husgafvel-Pursiainen K., Karjalainen A., Anttila S., Vainio H. Point-mutational MspI and Ile-Val polymorphisms closely linked in the CYP1A1 gene: lack of association with susceptibility to lung cancer in a Finnish study population. Cancer Epidemiol Biomarkers Prev. 1992 Sep-Oct;1(6):485–489. [PubMed] [Google Scholar]
  62. Hizuka N., Gorden P., Lesniak M. A., Van Obberghen E., Carpentier J. L., Orci L. Polypeptide hormone degradation and receptor regulation are coupled to ligand internalization. A direct biochemical and morphologic demonstration. J Biol Chem. 1981 May 10;256(9):4591–4597. [PubMed] [Google Scholar]
  63. Häussinger D., Stehle T., Gerok W., Tran-Thi T. A., Decker K. Hepatocyte heterogeneity in response to extracellular ATP. Eur J Biochem. 1987 Dec 15;169(3):645–650. doi: 10.1111/j.1432-1033.1987.tb13656.x. [DOI] [PubMed] [Google Scholar]
  64. Häussinger D., Stehle T. Hepatocyte heterogeneity in response to icosanoids. The perivenous scavenger cell hypothesis. Eur J Biochem. 1988 Aug 1;175(2):395–403. doi: 10.1111/j.1432-1033.1988.tb14209.x. [DOI] [PubMed] [Google Scholar]
  65. Ingelman-Sundberg M., Johansson I., Penttilä K. E., Glaumann H., Lindros K. O. Centrilobular expression of ethanol-inducible cytochrome P-450 (IIE1) in rat liver. Biochem Biophys Res Commun. 1988 Nov 30;157(1):55–60. doi: 10.1016/s0006-291x(88)80010-x. [DOI] [PubMed] [Google Scholar]
  66. Johansson I., Ekström G., Scholte B., Puzycki D., Jörnvall H., Ingelman-Sundberg M. Ethanol-, fasting-, and acetone-inducible cytochromes P-450 in rat liver: regulation and characteristics of enzymes belonging to the IIB and IIE gene subfamilies. Biochemistry. 1988 Mar 22;27(6):1925–1934. doi: 10.1021/bi00406a019. [DOI] [PubMed] [Google Scholar]
  67. Johansson I., Lindros K. O., Eriksson H., Ingelman-Sundberg M. Transcriptional control of CYP2E1 in the perivenous liver region and during starvation. Biochem Biophys Res Commun. 1990 Nov 30;173(1):331–338. doi: 10.1016/s0006-291x(05)81061-7. [DOI] [PubMed] [Google Scholar]
  68. Jungermann K., Katz N. Functional specialization of different hepatocyte populations. Physiol Rev. 1989 Jul;69(3):708–764. doi: 10.1152/physrev.1989.69.3.708. [DOI] [PubMed] [Google Scholar]
  69. Jungermann K. Zonation of metabolism and gene expression in liver. Histochem Cell Biol. 1995 Feb;103(2):81–91. doi: 10.1007/BF01454004. [DOI] [PubMed] [Google Scholar]
  70. Kamataki T., Maeda K., Yamazoe Y., Matsuda N., Ishii K., Kato R. A high-spin form of cytochrome P-450 highly purified from polychlorinated biphenyl-treated rats. Catalytic characterization and immunochemical quantitation in liver microsomes. Mol Pharmacol. 1983 Jul;24(1):146–155. [PubMed] [Google Scholar]
  71. Kamataki T., Shimada M., Maeda K., Kato R. Pituitary regulation of sex-specific forms of cytochrome P-450 in liver microsomes of rats. Biochem Biophys Res Commun. 1985 Aug 15;130(3):1247–1253. doi: 10.1016/0006-291x(85)91748-6. [DOI] [PubMed] [Google Scholar]
  72. Kanai K., Watanabe J., Kanamura S. Quantitative analysis of smooth and rough endoplasmic reticulum proliferation in differentiating hepatocytes of midpostnatal mice treated with phenobarbital. J Ultrastruct Mol Struct Res. 1986 Oct-Dec;97(1-3):64–72. doi: 10.1016/s0889-1605(86)80007-6. [DOI] [PubMed] [Google Scholar]
  73. Kawajiri K., Nakachi K., Imai K., Yoshii A., Shinoda N., Watanabe J. Identification of genetically high risk individuals to lung cancer by DNA polymorphisms of the cytochrome P450IA1 gene. FEBS Lett. 1990 Apr 9;263(1):131–133. doi: 10.1016/0014-5793(90)80721-t. [DOI] [PubMed] [Google Scholar]
  74. Kellermann G., Shaw C. R., Luyten-Kellerman M. Aryl hydrocarbon hydroxylase inducibility and bronchogenic carcinoma. N Engl J Med. 1973 Nov 1;289(18):934–937. doi: 10.1056/NEJM197311012891802. [DOI] [PubMed] [Google Scholar]
  75. Kera Y., Penttilä K. E., Lindros K. O. Glutathione replenishment capacity is lower in isolated perivenous than in periportal hepatocytes. Biochem J. 1988 Sep 1;254(2):411–417. doi: 10.1042/bj2540411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Kera Y., Sippel H. W., Penttilä K. E., Lindros K. O. Acinar distribution of glutathione-dependent detoxifying enzymes. Low glutathione peroxidase activity in perivenous hepatocytes. Biochem Pharmacol. 1987 Jun 15;36(12):2003–2006. doi: 10.1016/0006-2952(87)90500-4. [DOI] [PubMed] [Google Scholar]
  77. Kietzmann T., Schmidt H., Probst I., Jungermann K. Modulation of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene by oxygen in rat hepatocyte cultures. Evidence for a heme protein as oxygen sensor. FEBS Lett. 1992 Oct 26;311(3):251–255. doi: 10.1016/0014-5793(92)81113-z. [DOI] [PubMed] [Google Scholar]
  78. Kietzmann T., Schmidt H., Unthan-Fechner K., Probst I., Jungermann K. A ferro-heme protein senses oxygen levels, which modulate the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures. Biochem Biophys Res Commun. 1993 Sep 15;195(2):792–798. doi: 10.1006/bbrc.1993.2115. [DOI] [PubMed] [Google Scholar]
  79. Kirby G. M., Pelkonen P., Vatanasapt V., Camus A. M., Wild C. P., Lang M. A. Association of liver fluke (Opisthorchis viverrini) infestation with increased expression of cytochrome P450 and carcinogen metabolism in male hamster liver. Mol Carcinog. 1994 Oct;11(2):81–89. doi: 10.1002/mc.2940110205. [DOI] [PubMed] [Google Scholar]
  80. Kouri R. E., McKinney C. E., Slomiany D. J., Snodgrass D. R., Wray N. P., McLemore T. L. Positive correlation between high aryl hydrocarbon hydroxylase activity and primary lung cancer as analyzed in cryopreserved lymphocytes. Cancer Res. 1982 Dec;42(12):5030–5037. [PubMed] [Google Scholar]
  81. Landers J. P., Bunce N. J. The Ah receptor and the mechanism of dioxin toxicity. Biochem J. 1991 Jun 1;276(Pt 2):273–287. doi: 10.1042/bj2760273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Legraverend C., Eguchi H., Ström A., Lahuna O., Mode A., Tollet P., Westin S., Gustafsson J. A. Transactivation of the rat CYP2C13 gene promoter involves HNF-1, HNF-3, and members of the orphan receptor subfamily. Biochemistry. 1994 Aug 23;33(33):9889–9897. doi: 10.1021/bi00199a010. [DOI] [PubMed] [Google Scholar]
  83. Legraverend C., Mode A., Wells T., Robinson I., Gustafsson J. A. Hepatic steroid hydroxylating enzymes are controlled by the sexually dimorphic pattern of growth hormone secretion in normal and dwarf rats. FASEB J. 1992 Jan 6;6(2):711–718. doi: 10.1096/fasebj.6.2.1537461. [DOI] [PubMed] [Google Scholar]
  84. Legraverend C., Mode A., Westin S., Ström A., Eguchi H., Zaphiropoulos P. G., Gustafsson J. A. Transcriptional regulation of rat P-450 2C gene subfamily members by the sexually dimorphic pattern of growth hormone secretion. Mol Endocrinol. 1992 Feb;6(2):259–266. doi: 10.1210/mend.6.2.1569969. [DOI] [PubMed] [Google Scholar]
  85. Liddle C., Mode A., Legraverend C., Gustafsson J. A. Constitutive expression and hormonal regulation of male sexually differentiated cytochromes P450 in primary cultured rat hepatocytes. Arch Biochem Biophys. 1992 Oct;298(1):159–166. doi: 10.1016/0003-9861(92)90107-8. [DOI] [PubMed] [Google Scholar]
  86. Lindros K. O., Oinonen T., Issakainen J., Nagy P., Thorgeirsson S. S. Zonal distribution of transcripts of four hepatic transcription factors in the mature rat liver. Cell Biol Toxicol. 1997 Jul;13(4-5):257–262. doi: 10.1023/a:1007479223229. [DOI] [PubMed] [Google Scholar]
  87. Lindros K. O., Oinonen T., Johansson I., Ingelman-Sundberg M. Selective centrilobular expression of the aryl hydrocarbon receptor in rat liver. J Pharmacol Exp Ther. 1997 Jan;280(1):506–511. [PubMed] [Google Scholar]
  88. Lindros K. O., Penttilä K. E. Digitonin-collagenase perfusion for efficient separation of periportal or perivenous hepatocytes. Biochem J. 1985 Jun 15;228(3):757–760. doi: 10.1042/bj2280757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Marti U., Gebhardt R. Acinar heterogeneity of the epidermal growth factor receptor in the liver of male rats. Eur J Cell Biol. 1991 Jun;55(1):158–164. [PubMed] [Google Scholar]
  90. McClellan-Green P. D., Linko P., Yeowell H. N., Goldstein J. A. Hormonal regulation of male-specific rat hepatic cytochrome P-450g (P-450IIC13) by androgens and the pituitary. J Biol Chem. 1989 Nov 15;264(32):18960–18965. [PubMed] [Google Scholar]
  91. McKay J. A., Melvin W. T., Ah-See A. K., Ewen S. W., Greenlee W. F., Marcus C. B., Burke M. D., Murray G. I. Expression of cytochrome P450 CYP1B1 in breast cancer. FEBS Lett. 1995 Oct 30;374(2):270–272. doi: 10.1016/0014-5793(95)01126-y. [DOI] [PubMed] [Google Scholar]
  92. Mendel C. M., Weisiger R. A., Jones A. L., Cavalieri R. R. Thyroid hormone-binding proteins in plasma facilitate uniform distribution of thyroxine within tissues: a perfused rat liver study. Endocrinology. 1987 May;120(5):1742–1749. doi: 10.1210/endo-120-5-1742. [DOI] [PubMed] [Google Scholar]
  93. Moody D. E., Taylor L. A., Smuckler E. A., Levin W., Thomas P. E. Immunohistochemical localization of cytochrome P-450a in liver sections from untreated rats and rats treated with phenobarbital or 3-methylcholanthrene. Drug Metab Dispos. 1983 Jul-Aug;11(4):339–343. [PubMed] [Google Scholar]
  94. Moorman A. F., van den Hoff M. J., de Boer P. A., Charles R., Lamers W. H. The dynamics of the expression of C/EBP mRNA in the adult rat liver lobulus qualifies it as a pericentral mRNA. FEBS Lett. 1991 Aug 19;288(1-2):133–137. doi: 10.1016/0014-5793(91)81019-5. [DOI] [PubMed] [Google Scholar]
  95. Morgan E. T., MacGeoch C., Gustafsson J. A. Hormonal and developmental regulation of expression of the hepatic microsomal steroid 16 alpha-hydroxylase cytochrome P-450 apoprotein in the rat. J Biol Chem. 1985 Oct 5;260(22):11895–11898. [PubMed] [Google Scholar]
  96. Murayama N., Shimada M., Yamazoe Y., Kato R. Difference in the susceptibility of two phenobarbital-inducible forms, P450IIB1 and P450IIB2, to thyroid hormone- and growth hormone-induced suppression in rat liver: phenobarbital-inducible P450IIB2 suppression by thyroid hormone acting directly, but not through the pituitary system. Mol Pharmacol. 1991 Jun;39(6):811–817. [PubMed] [Google Scholar]
  97. Murayama N., Shimada M., Yamazoe Y., Sogawa K., Nakayama K., Fujii-Kuriyama Y., Kato R. Distinct effects of phenobarbital and its N-methylated derivative on liver cytochrome P450 induction. Arch Biochem Biophys. 1996 Apr 1;328(1):184–192. doi: 10.1006/abbi.1996.0159. [DOI] [PubMed] [Google Scholar]
  98. Nakachi K., Imai K., Hayashi S., Kawajiri K. Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population. Cancer Res. 1993 Jul 1;53(13):2994–2999. [PubMed] [Google Scholar]
  99. Nakachi K., Imai K., Hayashi S., Watanabe J., Kawajiri K. Genetic susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose. Cancer Res. 1991 Oct 1;51(19):5177–5180. [PubMed] [Google Scholar]
  100. Nauck M., Wölfle D., Katz N., Jungermann K. Modulation of the glucagon-dependent induction of phosphoenolpyruvate carboxykinase and tyrosine aminotransferase by arterial and venous oxygen concentrations in hepatocyte cultures. Eur J Biochem. 1981 Oct;119(3):657–661. doi: 10.1111/j.1432-1033.1981.tb05658.x. [DOI] [PubMed] [Google Scholar]
  101. Nelson D. R., Kamataki T., Waxman D. J., Guengerich F. P., Estabrook R. W., Feyereisen R., Gonzalez F. J., Coon M. J., Gunsalus I. C., Gotoh O. The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol. 1993 Jan-Feb;12(1):1–51. doi: 10.1089/dna.1993.12.1. [DOI] [PubMed] [Google Scholar]
  102. Nelson D. R., Koymans L., Kamataki T., Stegeman J. J., Feyereisen R., Waxman D. J., Waterman M. R., Gotoh O., Coon M. J., Estabrook R. W. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics. 1996 Feb;6(1):1–42. doi: 10.1097/00008571-199602000-00002. [DOI] [PubMed] [Google Scholar]
  103. Noshiro M., Nishimoto M., Okuda K. Rat liver cholesterol 7 alpha-hydroxylase. Pretranslational regulation for circadian rhythm. J Biol Chem. 1990 Jun 15;265(17):10036–10041. [PubMed] [Google Scholar]
  104. Ohnishi K., Mishima A., Okuda K. Immunofluorescence of phenobarbital inducible cytochrome P-450 in the hepatic lobule of normal and phenobarbital-treated rats. Hepatology. 1982 Nov-Dec;2(6):849–855. doi: 10.1002/hep.1840020619. [DOI] [PubMed] [Google Scholar]
  105. Oinonen T., Lindros K. O. Hormonal regulation of the zonated expression of cytochrome P-450 3A in rat liver. Biochem J. 1995 Jul 1;309(Pt 1):55–61. doi: 10.1042/bj3090055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  106. Oinonen T., Mode A., Lobie P. E., Lindros K. O. Zonation of cytochrome P450 enzyme expression in rat liver. Isozyme-specific regulation by pituitary dependent hormones. Biochem Pharmacol. 1996 May 17;51(10):1379–1387. doi: 10.1016/0006-2952(96)00064-0. [DOI] [PubMed] [Google Scholar]
  107. Oinonen T., Nikkola E., Lindros K. O. Growth hormone mediates zone-specific gene expression in liver. FEBS Lett. 1993 Jul 26;327(2):237–240. doi: 10.1016/0014-5793(93)80176-u. [DOI] [PubMed] [Google Scholar]
  108. Oinonen T., Saarikoski S., Husgafvel-Pursiainen K., Hirvonen A., Lindros K. O. Pretranslational induction of cytochrome P4501A enzymes by beta-naphthoflavone and 3-methylcholanthrene occurs in different liver zones. Biochem Pharmacol. 1994 Dec 16;48(12):2189–2197. doi: 10.1016/0006-2952(94)00385-8. [DOI] [PubMed] [Google Scholar]
  109. Okey A. B., Bondy G. P., Mason M. E., Kahl G. F., Eisen H. J., Guenthner T. M., Nebert D. W. Regulatory gene product of the Ah locus. Characterization of the cytosolic inducer-receptor complex and evidence for its nuclear translocation. J Biol Chem. 1979 Nov 25;254(22):11636–11648. [PubMed] [Google Scholar]
  110. Okey A. B., Riddick D. S., Harper P. A. Molecular biology of the aromatic hydrocarbon (dioxin) receptor. Trends Pharmacol Sci. 1994 Jul;15(7):226–232. doi: 10.1016/0165-6147(94)90316-6. [DOI] [PubMed] [Google Scholar]
  111. Omiecinski C. J., Hassett C., Costa P. Developmental expression and in situ localization of the phenobarbital-inducible rat hepatic mRNAs for cytochromes CYP2B1, CYP2B2, CYP2C6, and CYP3A1. Mol Pharmacol. 1990 Oct;38(4):462–470. [PubMed] [Google Scholar]
  112. Oppenheimer J. H., Schwartz H. L., Surks M. I. Tissue differences in the concentration of triiodothyronine nuclear binding sites in the rat: liver, kidney, pituitary, heart, brain, spleen, and testis. Endocrinology. 1974 Sep;95(3):897–903. doi: 10.1210/endo-95-3-897. [DOI] [PubMed] [Google Scholar]
  113. Palmer C. N., Coates P. J., Davies S. E., Shephard E. A., Phillips I. R. Localization of cytochrome P-450 gene expression in normal and diseased human liver by in situ hybridization of wax-embedded archival material. Hepatology. 1992 Sep;16(3):682–687. doi: 10.1002/hep.1840160311. [DOI] [PubMed] [Google Scholar]
  114. Palmer C. N., Hsu M. H., Muerhoff A. S., Griffin K. J., Johnson E. F. Interaction of the peroxisome proliferator-activated receptor alpha with the retinoid X receptor alpha unmasks a cryptic peroxisome proliferator response element that overlaps an ARP-1-binding site in the CYP4A6 promoter. J Biol Chem. 1994 Jul 8;269(27):18083–18089. [PubMed] [Google Scholar]
  115. Pampori N. A., Shapiro B. H. Feminization of hepatic cytochrome P450s by nominal levels of growth hormone in the feminine plasma profile. Mol Pharmacol. 1996 Nov;50(5):1148–1156. [PubMed] [Google Scholar]
  116. Park Y., Li H., Kemper B. Phenobarbital induction mediated by a distal CYP2B2 sequence in rat liver transiently transfected in situ. J Biol Chem. 1996 Sep 27;271(39):23725–23728. doi: 10.1074/jbc.271.39.23725. [DOI] [PubMed] [Google Scholar]
  117. Parke D. V., Ioannides C., Lewis D. F. The 1990 Pharmaceutical Manufacturers Association of Canada keynote lecture. The role of the cytochromes P450 in the detoxication and activation of drugs and other chemicals. Can J Physiol Pharmacol. 1991 May;69(5):537–549. doi: 10.1139/y91-081. [DOI] [PubMed] [Google Scholar]
  118. Perdew G. H., Hollenback C. E. Analysis of photoaffinity-labeled aryl hydrocarbon receptor heterogeneity by two-dimensional gel electrophoresis. Biochemistry. 1990 Jul 3;29(26):6210–6214. doi: 10.1021/bi00478a014. [DOI] [PubMed] [Google Scholar]
  119. Petruzzelli S., Camus A. M., Carrozzi L., Ghelarducci L., Rindi M., Menconi G., Angeletti C. A., Ahotupa M., Hietanen E., Aitio A. Long-lasting effects of tobacco smoking on pulmonary drug-metabolizing enzymes: a case-control study on lung cancer patients. Cancer Res. 1988 Aug 15;48(16):4695–4700. [PubMed] [Google Scholar]
  120. Prabhu L., Upadhya P., Ram N., Nirodi C. S., Sultana S., Vatsala P. G., Mani S. A., Rangarajan P. N., Surolia A., Padmanaban G. A model for the transcriptional regulation of the CYP2B1/B2 gene in rat liver. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9628–9632. doi: 10.1073/pnas.92.21.9628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. Püschel G. P., Oppermann M., Neuschäfer-Rube F., Götze O., Jungermann K. Differential effects of human anaphylatoxin C3a on glucose output and flow in rat liver during orthograde and retrograde perfusion: the periportal scavenger cell hypothesis. Biochem Biophys Res Commun. 1991 May 15;176(3):1218–1226. doi: 10.1016/0006-291x(91)90415-4. [DOI] [PubMed] [Google Scholar]
  122. Quattrochi L. C., Mills A. S., Barwick J. L., Yockey C. B., Guzelian P. S. A novel cis-acting element in a liver cytochrome P450 3A gene confers synergistic induction by glucocorticoids plus antiglucocorticoids. J Biol Chem. 1995 Dec 1;270(48):28917–28923. doi: 10.1074/jbc.270.48.28917. [DOI] [PubMed] [Google Scholar]
  123. Quistorff B., Grunnet N. Dual-digitonin-pulse perfusion. Concurrent sampling of periportal and perivenous cytosol of rat liver for determination of metabolites and enzyme activities. Biochem J. 1987 Apr 1;243(1):87–95. doi: 10.1042/bj2430087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  124. Ram P. A., Park S. H., Choi H. K., Waxman D. J. Growth hormone activation of Stat 1, Stat 3, and Stat 5 in rat liver. Differential kinetics of hormone desensitization and growth hormone stimulation of both tyrosine phosphorylation and serine/threonine phosphorylation. J Biol Chem. 1996 Mar 8;271(10):5929–5940. doi: 10.1074/jbc.271.10.5929. [DOI] [PubMed] [Google Scholar]
  125. Ram P. A., Waxman D. J. Pretranslational control by thyroid hormone of rat liver steroid 5 alpha-reductase and comparison to the thyroid dependence of two growth hormone-regulated CYP2C mRNAs. J Biol Chem. 1990 Nov 5;265(31):19223–19229. [PubMed] [Google Scholar]
  126. Ramsden R., Sommer K. M., Omiecinski C. J. Phenobarbital induction and tissue-specific expression of the rat CYP2B2 gene in transgenic mice. J Biol Chem. 1993 Oct 15;268(29):21722–21726. [PubMed] [Google Scholar]
  127. Redick J. A., Kawabata T. T., Guengerich F. P., Krieter P. A., Shires T. K., Baron J. Distributions of monooxygenase components and epoxide hydratase within the livers of untreated male rats. Life Sci. 1980 Dec 22;27(25-26):2465–2470. doi: 10.1016/0024-3205(80)90523-8. [DOI] [PubMed] [Google Scholar]
  128. Rich K. J., Sesardic D., Foster J. R., Davies D. S., Boobis A. R. Immunohistochemical localization of cytochrome P450b/e in hepatic and extrahepatic tissues of the rat. Biochem Pharmacol. 1989 Oct 1;38(19):3305–3322. doi: 10.1016/0006-2952(89)90629-1. [DOI] [PubMed] [Google Scholar]
  129. Roe A. L., Blouin R. A., Howard G. In vivo phenobarbital treatment increases protein binding to a putative AP-1 site in the CYP2B2 promoter. Biochem Biophys Res Commun. 1996 Nov 1;228(1):110–114. doi: 10.1006/bbrc.1996.1624. [DOI] [PubMed] [Google Scholar]
  130. Saad B., Thomas H., Schawalder H., Waechter F., Maier P. Oxygen tension, insulin, and glucagon affect the preservation and induction of cytochrome P450 isoforms in cultured rat hepatocytes. Toxicol Appl Pharmacol. 1994 Jun;126(2):372–379. doi: 10.1006/taap.1994.1128. [DOI] [PubMed] [Google Scholar]
  131. Saarinen J., Saarelainen R., Lindros K. O. A rapid method to study heterogeneous gene expression in liver by direct assay of messenger RNA from periportal and perivenous cell lysates. Hepatology. 1993 Mar;17(3):466–469. [PubMed] [Google Scholar]
  132. Sasamura H., Nagata K., Yamazoe Y., Shimada M., Saruta T., Kato R. Effect of growth hormone on rat hepatic cytochrome P-450f mRNA: a new mode of regulation. Mol Cell Endocrinol. 1990 Jan 2;68(1):53–60. doi: 10.1016/0303-7207(90)90169-9. [DOI] [PubMed] [Google Scholar]
  133. Schrode W., Mecke D., Gebhardt R. Induction of glutamine synthetase in periportal hepatocytes by cocultivation with a liver epithelial cell line. Eur J Cell Biol. 1990 Oct;53(1):35–41. [PubMed] [Google Scholar]
  134. Schuetz E. G., Guzelian P. S. Induction of cytochrome P-450 by glucocorticoids in rat liver. II. Evidence that glucocorticoids regulate induction of cytochrome P-450 by a nonclassical receptor mechanism. J Biol Chem. 1984 Feb 10;259(3):2007–2012. [PubMed] [Google Scholar]
  135. Schuetz E. G., Schuetz J. D., May B., Guzelian P. S. Regulation of cytochrome P-450b/e and P-450p gene expression by growth hormone in adult rat hepatocytes cultured on a reconstituted basement membrane. J Biol Chem. 1990 Jan 15;265(2):1188–1192. [PubMed] [Google Scholar]
  136. Schwarz M., Peres G., Buchmann A., Friedberg T., Waxman D. J., Kunz W. Phenobarbital induction of cytochrome P-450 in normal and preneoplastic rat liver: comparison of enzyme and mRNA expression as detected by immunohistochemistry and in situ hybridization. Carcinogenesis. 1987 Sep;8(9):1355–1357. doi: 10.1093/carcin/8.9.1355. [DOI] [PubMed] [Google Scholar]
  137. Seibert B., Oesch F., Steinberg P. Distribution and induction of cytochrome P-450 and two cytochrome P-450-dependent monooxygenase activities in rat liver parenchymal cell subpopulations separated by centrifugal elutriation. Arch Toxicol. 1989;63(1):18–22. doi: 10.1007/BF00334628. [DOI] [PubMed] [Google Scholar]
  138. Shaw P. M., Adesnik M., Weiss M. C., Corcos L. The phenobarbital-induced transcriptional activation of cytochrome P-450 genes is blocked by the glucocorticoid-progesterone antagonist RU486. Mol Pharmacol. 1993 Oct;44(4):775–783. [PubMed] [Google Scholar]
  139. Shaw P. M., Weiss M. C., Adesnik M. Hepatocyte nuclear factor 3 is a major determinant of CYP2C6 promoter activity in hepatoma cells. Mol Pharmacol. 1994 Jul;46(1):79–87. [PubMed] [Google Scholar]
  140. Shephard E. A., Forrest L. A., Shervington A., Fernandez L. M., Ciaramella G., Phillips I. R. Interaction of proteins with a cytochrome P450 2B2 gene promoter: identification of two DNA sequences that bind proteins that are enriched or activated in response to phenobarbital. DNA Cell Biol. 1994 Aug;13(8):793–804. doi: 10.1089/dna.1994.13.793. [DOI] [PubMed] [Google Scholar]
  141. Shimada M., Murayama N., Nagata K., Hashimoto H., Ishikawa H., Yamazoe Y. A specific loss of growth hormone abolished sex-dependent expression of hepatic cytochrome P450 in dwarf rats: reversal of the profiles by growth hormone-treatment. Arch Biochem Biophys. 1997 Jan 1;337(1):34–42. doi: 10.1006/abbi.1996.9764. [DOI] [PubMed] [Google Scholar]
  142. Shimada M., Nagata K., Murayama N., Yamazoe Y., Kato R. Role of growth hormone in modulating the constitutive and phenobarbital-induced levels of two P-450(6)beta (testosterone 6 beta-hydroxylase) mRNAs in rat livers. J Biochem. 1989 Dec;106(6):1030–1034. doi: 10.1093/oxfordjournals.jbchem.a122959. [DOI] [PubMed] [Google Scholar]
  143. Shimojo N., Ishizaki T., Imaoka S., Funae Y., Fujii S., Okuda K. Changes in amounts of cytochrome P450 isozymes and levels of catalytic activities in hepatic and renal microsomes of rats with streptozocin-induced diabetes. Biochem Pharmacol. 1993 Aug 17;46(4):621–627. doi: 10.1016/0006-2952(93)90547-a. [DOI] [PubMed] [Google Scholar]
  144. Sidhu J. S., Omiecinski C. J. cAMP-associated inhibition of phenobarbital-inducible cytochrome P450 gene expression in primary rat hepatocyte cultures. J Biol Chem. 1995 May 26;270(21):12762–12773. doi: 10.1074/jbc.270.21.12762. [DOI] [PubMed] [Google Scholar]
  145. Sirma H., Williams G. M., Gebhardt R. Strain- and sex-specific variations in hepatic glutamine synthetase activity and distribution in rats and mice. Liver. 1996 Jun;16(3):166–173. doi: 10.1111/j.1600-0676.1996.tb00723.x. [DOI] [PubMed] [Google Scholar]
  146. Song B. J., Veech R. L., Park S. S., Gelboin H. V., Gonzalez F. J. Induction of rat hepatic N-nitrosodimethylamine demethylase by acetone is due to protein stabilization. J Biol Chem. 1989 Feb 25;264(6):3568–3572. [PubMed] [Google Scholar]
  147. St Hilaire R. J., Hradek G. T., Jones A. L. Hepatic sequestration and biliary secretion of epidermal growth factor: evidence for a high-capacity uptake system. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3797–3801. doi: 10.1073/pnas.80.12.3797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  148. Stoll B., Hüssinger D. Functional hepatocyte heterogeneity. Vascular 2-oxoglutarate is almost exclusively taken up by perivenous, glutamine-synthetase-containing hepatocytes. Eur J Biochem. 1989 May 15;181(3):709–716. doi: 10.1111/j.1432-1033.1989.tb14781.x. [DOI] [PubMed] [Google Scholar]
  149. Stravitz R. T., Hylemon P. B., Heuman D. M., Hagey L. R., Schteingart C. D., Ton-Nu H. T., Hofmann A. F., Vlahcevic Z. R. Transcriptional regulation of cholesterol 7 alpha-hydroxylase mRNA by conjugated bile acids in primary cultures of rat hepatocytes. J Biol Chem. 1993 Jul 5;268(19):13987–13993. [PubMed] [Google Scholar]
  150. Ström A. C., Forsberg M., Lillhager P., Westin G. The transcription factors Sp1 and Oct-1 interact physically to regulate human U2 snRNA gene expression. Nucleic Acids Res. 1996 Jun 1;24(11):1981–1986. doi: 10.1093/nar/24.11.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  151. Sundseth S. S., Waxman D. J. Sex-dependent expression and clofibrate inducibility of cytochrome P450 4A fatty acid omega-hydroxylases. Male specificity of liver and kidney CYP4A2 mRNA and tissue-specific regulation by growth hormone and testosterone. J Biol Chem. 1992 Feb 25;267(6):3915–3921. [PubMed] [Google Scholar]
  152. Suolinna E. M., Penttilä K. E., Winell B. M., Sjöholm A. C., Lindros K. O. Drug metabolism by periportal and perivenous rat hepatocytes. Comparison of phase I and phase II reactions and their inducibility during culture. Biochem Pharmacol. 1989 Apr 15;38(8):1329–1334. doi: 10.1016/0006-2952(89)90340-7. [DOI] [PubMed] [Google Scholar]
  153. Sutter T. R., Tang Y. M., Hayes C. L., Wo Y. Y., Jabs E. W., Li X., Yin H., Cody C. W., Greenlee W. F. Complete cDNA sequence of a human dioxin-inducible mRNA identifies a new gene subfamily of cytochrome P450 that maps to chromosome 2. J Biol Chem. 1994 May 6;269(18):13092–13099. [PubMed] [Google Scholar]
  154. Suwa Y., Mizukami Y., Sogawa K., Fujii-Kuriyama Y. Gene structure of a major form of phenobarbital-inducible cytochrome P-450 in rat liver. J Biol Chem. 1985 Jul 5;260(13):7980–7984. [PubMed] [Google Scholar]
  155. Swanson H. I., Bradfield C. A. The AH-receptor: genetics, structure and function. Pharmacogenetics. 1993 Oct;3(5):213–230. doi: 10.1097/00008571-199310000-00001. [DOI] [PubMed] [Google Scholar]
  156. Taira Y., Greenspan P., Kapke G. F., Redick J. A., Baron J. Effects of phenobarbital, pregnenolone-16 alpha-carbonitrile, and 3-methylcholanthrene pretreatments on the distribution of NADPH-cytochrome c (P-450) reductase within the liver lobule. Mol Pharmacol. 1980 Sep;18(2):304–312. [PubMed] [Google Scholar]
  157. Takahashi J. S. Circadian clock genes are ticking. Science. 1992 Oct 9;258(5080):238–240. doi: 10.1126/science.1384127. [DOI] [PubMed] [Google Scholar]
  158. Tannenbaum G. S., Martin J. B. Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Endocrinology. 1976 Mar;98(3):562–570. doi: 10.1210/endo-98-3-562. [DOI] [PubMed] [Google Scholar]
  159. Taylor P. M., Rennie M. J. Perivenous localisation of Na-dependent glutamate transport in perfused rat liver. FEBS Lett. 1987 Sep 14;221(2):370–374. doi: 10.1016/0014-5793(87)80958-4. [DOI] [PubMed] [Google Scholar]
  160. Tollet P., Enberg B., Mode A. Growth hormone (GH) regulation of cytochrome P-450IIC12, insulin-like growth factor-I (IGF-I), and GH receptor messenger RNA expression in primary rat hepatocytes: a hormonal interplay with insulin, IGF-I, and thyroid hormone. Mol Endocrinol. 1990 Dec;4(12):1934–1942. doi: 10.1210/mend-4-12-1934. [DOI] [PubMed] [Google Scholar]
  161. Tonda K., Hasegawa T., Hirata M. Effects of phenobarbital and 3-methylcholanthrene pretreatments on monooxygenase activities and proportions of isolated rat hepatocyte subpopulations. Mol Pharmacol. 1983 Jan;23(1):235–243. [PubMed] [Google Scholar]
  162. Tosh D., Borthwick E. B., Sharp S., Burchell A., Burchell B., Coughtrie M. W. Heterogeneous expression of sulphotransferases in periportal and perivenous hepatocytes prepared from male and female rat liver. Biochem Pharmacol. 1996 Feb 9;51(3):369–374. doi: 10.1016/0006-2952(95)02163-9. [DOI] [PubMed] [Google Scholar]
  163. Traber P. G., Maganto P., Wojcik E., Keren D., Gumucio J. J. Induction of P-450IIB genes within the rat liver acinus is not dependent on the chemical inducer or on the acinar organization. J Biol Chem. 1989 Jun 15;264(17):10292–10298. [PubMed] [Google Scholar]
  164. Tritscher A. M., Goldstein J. A., Portier C. J., McCoy Z., Clark G. C., Lucier G. W. Dose-response relationships for chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in a rat tumor promotion model: quantification and immunolocalization of CYP1A1 and CYP1A2 in the liver. Cancer Res. 1992 Jun 15;52(12):3436–3442. [PubMed] [Google Scholar]
  165. Trottier E., Belzil A., Stoltz C., Anderson A. Localization of a phenobarbital-responsive element (PBRE) in the 5'-flanking region of the rat CYP2B2 gene. Gene. 1995 Jun 9;158(2):263–268. doi: 10.1016/0378-1119(94)00916-g. [DOI] [PubMed] [Google Scholar]
  166. Tsukidate K., Sagami F., Horie T., Fukuda T., Kitada M., Kanakubo Y. Induction of cytochrome P-450 isozymes by chromanamine derivatives in rat liver. Xenobiotica. 1989 Aug;19(8):901–912. doi: 10.3109/00498258909043150. [DOI] [PubMed] [Google Scholar]
  167. Tukey R. H., Nebert D. W. Regulation of mouse cytochrome P3-450 by the Ah receptor. Studies with a P3-450 cDNA clone. Biochemistry. 1984 Dec 4;23(25):6003–6008. doi: 10.1021/bi00320a016. [DOI] [PubMed] [Google Scholar]
  168. Twisk J., Hoekman M. F., Lehmann E. M., Meijer P., Mager W. H., Princen H. M. Insulin suppresses bile acid synthesis in cultured rat hepatocytes by down-regulation of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase gene transcription. Hepatology. 1995 Feb;21(2):501–510. [PubMed] [Google Scholar]
  169. Twisk J., Hoekman M. F., Mager W. H., Moorman A. F., de Boer P. A., Scheja L., Princen H. M., Gebhardt R. Heterogeneous expression of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase genes in the rat liver lobulus. J Clin Invest. 1995 Mar;95(3):1235–1243. doi: 10.1172/JCI117773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  170. Twisk J., Lehmann E. M., Princen H. M. Differential feedback regulation of cholesterol 7 alpha-hydroxylase mRNA and transcriptional activity by rat bile acids in primary monolayer cultures of rat hepatocytes. Biochem J. 1993 Mar 15;290(Pt 3):685–691. doi: 10.1042/bj2900685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  171. Twisk J., de Wit E. C., Princen H. M. Suppression of sterol 27-hydroxylase mRNA and transcriptional activity by bile acids in cultured rat hepatocytes. Biochem J. 1995 Jan 15;305(Pt 2):505–511. doi: 10.1042/bj3050505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  172. Ueno T., Gonzalez F. J. Transcriptional control of the rat hepatic CYP2E1 gene. Mol Cell Biol. 1990 Sep;10(9):4495–4505. doi: 10.1128/mcb.10.9.4495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  173. Ugele B., Kempen H. J., Kempen J. M., Gebhardt R., Meijer P., Burger H. J., Princen H. M. Heterogeneity of rat liver parenchyma in cholesterol 7 alpha-hydroxylase and bile acid synthesis. Biochem J. 1991 May 15;276(Pt 1):73–77. doi: 10.1042/bj2760073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  174. Visser T. J. A tentative review of recent in vitro observations of the enzymatic deiodination of iodothyronines and its possible physiological implications. Mol Cell Endocrinol. 1978 May;10(3):241–247. doi: 10.1016/0303-7207(78)90039-4. [DOI] [PubMed] [Google Scholar]
  175. Waxman D. J., Azaroff L. Phenobarbital induction of cytochrome P-450 gene expression. Biochem J. 1992 Feb 1;281(Pt 3):577–592. doi: 10.1042/bj2810577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  176. Waxman D. J. Interactions of hepatic cytochromes P-450 with steroid hormones. Regioselectivity and stereospecificity of steroid metabolism and hormonal regulation of rat P-450 enzyme expression. Biochem Pharmacol. 1988 Jan 1;37(1):71–84. doi: 10.1016/0006-2952(88)90756-3. [DOI] [PubMed] [Google Scholar]
  177. Waxman D. J., LeBlanc G. A., Morrissey J. J., Staunton J., Lapenson D. P. Adult male-specific and neonatally programmed rat hepatic P-450 forms RLM2 and 2a are not dependent on pulsatile plasma growth hormone for expression. J Biol Chem. 1988 Aug 15;263(23):11396–11406. [PubMed] [Google Scholar]
  178. Waxman D. J., Morrissey J. J., LeBlanc G. A. Female-predominant rat hepatic P-450 forms j (IIE1) and 3 (IIA1) are under hormonal regulatory controls distinct from those of the sex-specific P-450 forms. Endocrinology. 1989 Jun;124(6):2954–2966. doi: 10.1210/endo-124-6-2954. [DOI] [PubMed] [Google Scholar]
  179. Waxman D. J., Pampori N. A., Ram P. A., Agrawal A. K., Shapiro B. H. Interpulse interval in circulating growth hormone patterns regulates sexually dimorphic expression of hepatic cytochrome P450. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6868–6872. doi: 10.1073/pnas.88.15.6868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  180. Waxman D. J., Ram P. A., Notani G., LeBlanc G. A., Alberta J. A., Morrissey J. J., Sundseth S. S. Pituitary regulation of the male-specific steroid 6 beta-hydroxylase P-450 2a (gene product IIIA2) in adult rat liver. Suppressive influence of growth hormone and thyroxine acting at a pretranslational leve;. Mol Endocrinol. 1990 Mar;4(3):447–454. doi: 10.1210/mend-4-3-447. [DOI] [PubMed] [Google Scholar]
  181. Waxman D. J., Ram P. A., Pampori N. A., Shapiro B. H. Growth hormone regulation of male-specific rat liver P450s 2A2 and 3A2: induction by intermittent growth hormone pulses in male but not female rats rendered growth hormone deficient by neonatal monosodium glutamate. Mol Pharmacol. 1995 Nov;48(5):790–797. [PubMed] [Google Scholar]
  182. Waxman D. J., Ram P. A., Park S. H., Choi H. K. Intermittent plasma growth hormone triggers tyrosine phosphorylation and nuclear translocation of a liver-expressed, Stat 5-related DNA binding protein. Proposed role as an intracellular regulator of male-specific liver gene transcription. J Biol Chem. 1995 Jun 2;270(22):13262–13270. doi: 10.1074/jbc.270.22.13262. [DOI] [PubMed] [Google Scholar]
  183. Waxman D. J., Walsh C. Phenobarbital-induced rat liver cytochrome P-450. Purification and characterization of two closely related isozymic forms. J Biol Chem. 1982 Sep 10;257(17):10446–10457. [PubMed] [Google Scholar]
  184. Waxman D. J., Zhao S., Choi H. K. Interaction of a novel sex-dependent, growth hormone-regulated liver nuclear factor with CYP2C12 promoter. J Biol Chem. 1996 Nov 22;271(47):29978–29987. doi: 10.1074/jbc.271.47.29978. [DOI] [PubMed] [Google Scholar]
  185. Weisiger R. A., Mendel C. M., Cavalieri R. R. The hepatic sinusoid is not well-stirred: estimation of the degree of axial mixing by analysis of lobular concentration gradients formed during uptake of thyroxine by the perfused rat liver. J Pharm Sci. 1986 Mar;75(3):233–237. doi: 10.1002/jps.2600750304. [DOI] [PubMed] [Google Scholar]
  186. Westin S., Ström A., Gustafsson J. A., Zaphiropoulos P. G. Growth hormone regulation of the cytochrome P-450IIC subfamily in the rat: inductive, repressive, and transcriptional effects on P-450f (IIC7) and P-450PB1 (IIC6) gene expression. Mol Pharmacol. 1990 Aug;38(2):192–197. [PubMed] [Google Scholar]
  187. Whitlock J. P., Jr The regulation of gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Pharmacol Rev. 1987 Jun;39(2):147–161. [PubMed] [Google Scholar]
  188. Williams M. T., Simonet L. C. Effects of growth hormone on cytochrome P-450j. Biochem Biophys Res Commun. 1988 Aug 30;155(1):392–397. doi: 10.1016/s0006-291x(88)81098-2. [DOI] [PubMed] [Google Scholar]
  189. Willson R. A., Liem H. H., Miyai K., Muller-Eberhard U. Heterogeneous distribution of drug metabolism in elutriated rat hepatocytes. Biochem Pharmacol. 1985 May 1;34(9):1463–1470. doi: 10.1016/0006-2952(85)90685-9. [DOI] [PubMed] [Google Scholar]
  190. Wojcik E., Dvorak C., Chianale J., Traber P. G., Keren D., Gumucio J. J. Demonstration by in situ hybridization of the zonal modulation of rat liver cytochrome P-450b and P-450e gene expression after phenobarbital. J Clin Invest. 1988 Aug;82(2):658–666. doi: 10.1172/JCI113645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  191. Wolf C. R., Moll E., Friedberg T., Oesch F., Buchmann A., Kuhlmann W. D., Kunz H. W. Characterization, localization and regulation of a novel phenobarbital-inducible form of cytochrome P450, compared with three further P450-isoenzymes, NADPH P450-reductase, glutathione transferases and microsomal epoxide hydrolase. Carcinogenesis. 1984 Aug;5(8):993–1001. doi: 10.1093/carcin/5.8.993. [DOI] [PubMed] [Google Scholar]
  192. Wright M. C., Paine A. J. Induction of the cytochrome P450 3A subfamily in rat liver correlates with the binding of inducers to a microsomal protein. Biochem Biophys Res Commun. 1994 Jun 15;201(2):973–979. doi: 10.1006/bbrc.1994.1797. [DOI] [PubMed] [Google Scholar]
  193. Wright M. C., Wang X. J., Pimenta M., Ribeiro V., Paine A. J., Lechner M. C. Glucocorticoid receptor-independent transcriptional induction of cytochrome P450 3A1 by metyrapone and its potentiation by glucocorticoid. Mol Pharmacol. 1996 Oct;50(4):856–863. [PubMed] [Google Scholar]
  194. Xu X., Kelsey K. T., Wiencke J. K., Wain J. C., Christiani D. C. Cytochrome P450 CYP1A1 MspI polymorphism and lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev. 1996 Sep;5(9):687–692. [PubMed] [Google Scholar]
  195. Yamazoe Y., Ling X., Murayama N., Gong D., Nagata K., Kato R. Modulation of hepatic level of microsomal testosterone 7 alpha-hydroxylase, P-450a (P450IIA), by thyroid hormone and growth hormone in rat liver. J Biochem. 1990 Oct;108(4):599–603. doi: 10.1093/oxfordjournals.jbchem.a123249. [DOI] [PubMed] [Google Scholar]
  196. Yamazoe Y., Murayama N., Shimada M., Kato R. Thyroid hormone suppression of hepatic levels of phenobarbital-inducible P-450b and P-450e and other neonatal P-450s in hypophysectomized rats. Biochem Biophys Res Commun. 1989 Apr 28;160(2):609–614. doi: 10.1016/0006-291x(89)92476-5. [DOI] [PubMed] [Google Scholar]
  197. Yamazoe Y., Shimada M., Murayama N., Kato R. Suppression of levels of phenobarbital-inducible rat liver cytochrome P-450 by pituitary hormone. J Biol Chem. 1987 May 25;262(15):7423–7428. [PubMed] [Google Scholar]
  198. Yano M., Falvey E., Gonzalez F. J. Role of the liver-enriched transcription factor DBP in expression of the cytochrome P450 CYP2C6 gene. Mol Cell Biol. 1992 Jun;12(6):2847–2854. doi: 10.1128/mcb.12.6.2847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  199. Yoshida Y., Kimura N., Oda H., Kakinuma A. Insulin suppresses the induction of CYP2B1 and CYP2B2 gene expression by phenobarbital in adult rat cultured hepatocytes. Biochem Biophys Res Commun. 1996 Dec 4;229(1):182–188. doi: 10.1006/bbrc.1996.1777. [DOI] [PubMed] [Google Scholar]
  200. van Sliedregt A., van Bezooijen C. F. Effect of different doses of 3-methylcholanthrene on the localization of the 3-methylcholanthrene-inducible isoenzymes of cytochrome P450 within the centrilobular and periportal zones of the rat liver. Biochem Pharmacol. 1990 Jun 1;39(11):1703–1708. doi: 10.1016/0006-2952(90)90114-z. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES