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Inhibitory effect of androgen on the constitutive gene expression of hepatic drug metabolizing enzymes and its mechanism

Research Project

Project/Area Number 22590166
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionNational Institute of Agrobiological Sciences

Principal Investigator

KOJIMA Misaki  独立行政法人農業生物資源研究所, 家畜ゲノム研究ユニット, 上級研究員 (80355742)

Co-Investigator(Renkei-kenkyūsha) DEGAWA Masakuni  静岡県立大学, 薬学部, 教授 (50134002)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsアンドロゲン / 薬物代謝酵素 / 肝臓 / CYP / 性差 / 系統差 / 優性遺伝 / ブタ / 第II相薬物代謝酵素 / 構成的発現 / IL-1 / Cyp7a1 / PGC-1α / アンドロゲン濃度 / 常染色体性優性遺伝 / 転写因子 / CYP1A1 / CYP1A2 / 品種間差
Research Abstract

Sex differences in the constitutive expression of hepatic drug metabolizing enzymes, including cytochrome P4501A (CYP1A) subfamily enzymes, in the pig liver have been examined using 5-month-old Meishan, Landrace, and their F1 cross breeds, LM and ML pigs. The levels of serum androgen in all the pigs used were also examined, and the relationship between the serum androgen levels and the expression levels of hepatic metabolizing enzymes, which were observed to be expressed in a sex-dependent manner, were investigated. All the results indicated that serum andorogen down-regulated the constitutive gene expression of several drug metabolizing enzymes including CYP1As with threshold. Furthermore, it was demonstrated for the first time that serum androgen level in male pigs was determined by autosomal dominat inheritance.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (11 results)

All 2013 2012 2011 2010 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (6 results)

  • [Journal Article] Serum androgen level is determined by autosomal dominant inheritance and regulates sexrelated CYP genes in pigs2013

    • Author(s)
      M. Kojima and M. Degawa
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 430 Issue: 2 Pages: 833-838

    • DOI

      10.1016/j.bbrc.2012.11.060

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Interleukin-1 in Lead Nitrate-Induced Hypercholesterolemia in Mice2012

    • Author(s)
      M.Kojima
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 35 Issue: 2 Pages: 246-250

    • DOI

      10.1248/bpb.35.246

    • NAID

      130001872300

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-1 Controls the Constitutive Expression of the Cyp7a1 Gene by Regulating the Expression of Cyp7a1 Transcriptional Regulators in the Mouse Liver2011

    • Author(s)
      M.Kojima
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 34 Issue: 10 Pages: 1644-1647

    • DOI

      10.1248/bpb.34.1644

    • NAID

      130001086603

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Androgn-mediated down-regulation of CYP1A subfamily genes in the pig liver2010

    • Author(s)
      M. Kojima, M. Sekimoto and M. Degawa
    • Journal Title

      J. Endocrinol

      Volume: 207 Pages: 203-211

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Androgen-mediated down-regulation of CYP1A subfamily genes in the pig liver2010

    • Author(s)
      M.Kojima, M.Sekimoto, M.Degawa
    • Journal Title

      J.Endocrinol

      Volume: 207 Pages: 203-211

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Sex-differences in the constitutive gene expression levels of CYPs in the pig liver2012

    • Author(s)
      Misaki Kojima, Masashi Sekimoto, Masakuni Degawa
    • Organizer
      Androgen-mediated downregulation. 50th Anniversary Symposium on Cytochrome
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-03
    • Related Report
      2012 Final Research Report
  • [Presentation] マウス肝でのcholesterol 7α-hydroxylaseおよびその転写因子の構成的遺伝子発現におけるInterleulin-1の寄与2012

    • Author(s)
      小島美咲、芦野隆、吉田武美、岩倉洋一郎、関本征史、出川雅邦
    • Organizer
      フォーラム2012:衛生薬学・環境トキシコロジー
    • Place of Presentation
      名古屋
    • Year and Date
      2012-10-25
    • Related Report
      2012 Final Research Report
  • [Presentation] ブタにおける血清中アンドロゲン濃度は遺伝的に規定され、肝CYP1A酵素遺伝子の発現に影響を与える2011

    • Author(s)
      小島美咲、出川雅邦
    • Organizer
      第84回日本生化学会
    • Place of Presentation
      京都
    • Year and Date
      2011-09-22
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] ブタの肝臓における構成的CYP2およびCYP3ファミリー酵素の遺伝子発現に及ぼすアンドロゲンの影響2011

    • Author(s)
      小島美咲、出川雅邦
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-30
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Presentation] マウス肝でのcholetserol 7α-hydroxylaseおよびその転写因子の構成的遺伝子発現におけるInterleulin-1の寄与

    • Author(s)
      小島美咲、芦野隆、吉田武美、岩倉洋一郎、関本征史、出川雅邦
    • Organizer
      フォーラム2012:衛生薬学・環境トキシコロジー
    • Place of Presentation
      名古屋
    • Related Report
      2012 Annual Research Report
  • [Presentation] Sex-differences in the constitutive gene expression levels of CYPs in the pig liver: Androgen-mediated Dwonregulation

    • Author(s)
      M. Koima, M. Sekimoto and M. Degawa
    • Organizer
      50th Anniversary Symposium on Cytochrome P450 in Fukuoka
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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