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Analysis of sex hormone-responsive element in sexually dimorphicly expressing CYP2B subfamily gene

Research Project

Project/Area Number 10672105
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

NEMOTO Nobuo  TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY, Faculty of Pharmaceutical Sciences Professor, 薬学部, 教授 (10085631)

Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsCYP2B / Sex hormone / Glucocorticoid hormone / Phenobarbital / 肝細胞初代培養系 / マウス肝細胞初代培養系
Research Abstract

CYP2B subfamily constitutively and sexually dimorphicly expresses in the liver. In the mouse, the expression in female is far higher than that in male and the expressed species are different between male (Crp2b10>Cyp2b9) and female (Cyp2b9>Cyp2b10). The expression of these species is inducible by phenobarbital (PB), and the induction mechanism has been extensively revealed at molecular level. However, the mechanism of their constitutive expression has been scarcely investigated.
Female and glucocorticoid hormones may participate the expression of Cyp2b9 and Cyp2b10, respecitively, and the latter hormone simultaneously suppresses Cyp2b9 expression. The role of male hormone is also considered to suppress Cyp2b9 expression. The sequence from -2331 to -2281 bp of the 5'-flanking region of Cyp2b10 gene is revealed to be responsible for the estradiol induction using luciferase assay. This region corresponds to the core element of PB-responsive enhancer module (PBREM). Several nucleotide mutations in the PBREM core element show that the NR1 (nuclear receptor 1) site is required for estradiol induction, the same element required for PB induction. The element also plays a critical role for induction by DDT, indicating that NR1 site responds to structurally-diversed inducers. Although Cyp2b9 is a major species expressed in female liver, no information is available for its expression mechanism, but estradiol is found as a potent inducer for investigating of the regulatory pathway.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Sakuma T et al.: "Induction of CYP1A2 by phenobarbital in the livers of aryl hydrocarbon-responsive and -nonresponsive mice."Drug Metabol Dispos. 27巻. 379-384 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyamoto M et al.: "CYP2A6 gene deletion reduces susceptibility to lung cancer."Biochem Biophys Res Commun. 261巻. 658-660 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jarukamjorn K et al.: "Different regulation of the expression of mouse hepatic cytochrome P4502B enzymes by glucocorticoid and phenobarbital."Arch Biochem Biophys. 369巻. 89-99 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakuma T et al.: "A novel female-specific member of the CYP3A gene subfamily in the mouse liver."Arch Biochem Biophys. 377巻. 153-162 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jarkumjorn K et al.: "Discriminating activation of CYP2B9 expression in male C57BL/6 mouse liver by β-estradiol."Biochem Biophys Res Commun. 279巻. 288-292 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jarukamjorn K et al.: "Sex-associated expression of the mouse hepatic and renal CYP2B enzymes by glucocorticoid hormone."Biochem Pharmacol. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakuma T et al.: "Induction of CYP1A2 by phenobarbital in the livers of aryl hydrocarbon-responsive and -nonresponsive mice."Drug Metabol Dispos. 27. 379-384 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyamoto M et al.: "CYP2A6 gene deletion reduces susceptibility to lung cancer."Biochem Biophys Res Commun. 261. 658-660 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jarukamjorn K et al.: "Different regulation of the expression of mouse hepatic cytochrome P450 2B enzymes by glucocorticoid and phenobarbital."Arch Biochem Biophys. 369. 89-99 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakuma T et al.: "A novel female-specific member of the CYP3A gene subfamily in the mouse liver."Arch Biochem Biophys. 377. 153-162 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jarkumjorn K et al.: "Discriminating activation of CYP2B9 expression in male C57BL/6 mouse liver by β-estradiol."Biochem Biophys Res Commun. 279. 288-292 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jarukamjorn K et al.: "Sex-associated expression of the mouse hepatic and renal CYP2B enzymes by glucocorticoid hormone."Biochem Pharmacol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakuma T et al.: "A novel female-specific member of the CYP3A gene subfamily in the mouse liver."Arch Biochem Biophys. 377巻. 153-162 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Jarkumjorn K et al.: "Discriminating activation of CYP2B9 expression in male C57BL/6 mouse liver by β-estradiol."Biochem Biophys Res Commun. 279巻. 288-292 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Jarukamjorn K et al.: "Sex-associated expression of the mouse hepatic and renal CYP2B enzymes by glucocorticoid hormone."Biochem Pharmacol. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamamoto M et al.: "Localization of estradiol-responsive region in the phenobarbital-responsive enhancer module of mouse Cyp2b10 gene."J Biochem Mol Toxicol. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakuma T, Ohtake M, Katsurayama Y, Jarukamjorn K, Nemoto N.: "Induction of CYP1A2 by phenobarbital in the livers of aryl hydrocarbon-responsive and -nonresponsive mice."Drug Metabol Dispos. 27. 379-384 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Jarukamjorn K, Sakuma T, Miyaura J, Nemoto N.: "Different regulation of the expression of mouse hepatic cytochrome P450 2B enzymes by glucocorticoid and phenobarbital."Arch Biochem Biophys. 369. 89-99 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyamoto M, Umetsu Y, Dosaka-Akita H, Sawamura Y, Yokota J, Kunitoh H, Nemoto N, Sato K, Ariyoshi N, Kamataki T.: "CYP2A6 gene deletion reduces susceptibility to lung cancer."Biochem Biophys Res Commun. 261. 658-660 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Chida M, Yokoi T, Nemoto N, Inaba M, Kinoshita M, Kamataki T.: "A new variant CYP2D6 allele(CYP2D6^*21) with a single base insertion in exon 5 in Japanese population associated with a poor metabolizer phenotype."Pharmacogenetics. 9. 287-293 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Li H, Miyahara T, Tezuka Y, Namba T, Suzuki T, Dowaki R, Watanabe M, Nemoto N, Tonami S, Seto H, Kadota S.: "The effect of Kampo formulae on bone resorption in vitro and in vivo. II .Detailed study of berberine."Biol Pharm Bull. 22. 391-396 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyahara T, Harada M, Kozakai A, Matsumoto M, Hashimoto K, Inoue H, Yoda K, Nakatsu T, Kajita S, Yamazaki R, Higuchi S, Kozuka H, Nemoto N.: "Comparison of 26,27-hexafluoro-1α,25-dihydroxyvitamin D_3 and 1α,25-dihydroxyvitamin D_3 on the resorption of bone explants ex vivo."J Nur Sci Vitaminol. 45. 239-249 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sakuma T,Ohtake M,Jarukamjorn K,Nemoto N: "Induction of CYPlA2 by phenobarbital in the livers of arylhydrocarbon-responsive and-nonresponsive mice." Drug Metabol.Dispo.In press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Sakuma T,Hieda M,Ohgiya S,Nagata R,Nemoto N,Kamataki T: "Molecular cloning and functional analysis of cynomolgus monkey CYPIA2." Biochem.Pharmacol.56. 131-139 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Chida,M,Yokoi T,Nemoto N,Inaba M,Kinoshita M,Kamataki: "A new variant CYP2D6 allele(CYP2D6/C8)with a single base insertion in exon 5 in Japanese population associated with the poor metabolizer phenotype." Pharmacogenetics. in press.

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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