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Development of New Screening Method for Endocrine Disruptors and Analyses of Disrupting Mechanisms

Research Project

Project/Area Number 11557198
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Environmental pharmacy
Research InstitutionGraduate School of Pharmaceutical Sciences, Nagoya City University (2000-2002)
Osaka University (1999)

Principal Investigator

IMAGAWA Masayoshi  Nagoya City Univ., Pharm. Sci., Prof., 大学院・薬学研究科, 教授 (20136823)

Co-Investigator(Kenkyū-buntansha) NISHIKAWA Jun-ichi  Osaka Univ., Pharm. Sci., Assoc. Prof., 大学院・薬学研究科, 助教授 (90218131)
TSUKAMOTO Kikuo  Nagoya City Univ., Pharm. Sci., Assist. Prof., 大学院・薬学研究科, 講師 (20183478)
TAGUCHI Ryo  Nagoya City Univ., Pharm. Sci., Assoc. Prof., 大学院・薬学研究科, 助教授 (20080210)
NISHIHARA Tsutomu  Osaka Univ., Pharm. Sci., Prof., 大学院・薬学研究科, 教授 (50028859)
SAITO Koichi  Sumitomo Chemical Co. Ltd., Senior Scientist, 主任研究員
松尾 昌季  株式会社 住友化学工業, 研究主幹
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2002: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥3,200,000 (Direct Cost: ¥3,200,000)
Keywordsendocrine disruptors / estrogen receptor / cofactor / yeast / screening method / nuclear receptor
Research Abstract

The endocrine systems are involved in the multitude of physiological processes. Recently, the endocrine disrupting chemicals are thought to have some effects in these processes. Therefore, it is important to develop a screening method for chemicals having these activities, and also characterize a disrupting mechanism.
1) We developed a new screening method for chemicals having hormonal activities using yeast two-hybrid system.
2) Using this assay system, we tested more than five hundred chemicals and discussed the structure-activity relationship.
3) We demonstrated that PPAR_γ (peroxisome proliferator-activated receptor γ), which is one of the nuclesr receptor, has dual DNA binding specificity. When PPARγ makes homodimer binds to estrogen receptor binding sequences rather than direct repeat.
4) We established PPARγ-expressing cells. Using this cell line, we isolated the new target genes of PPARγ using subtraction protocol and two-dimensional electrophoresis.

Report

(5 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Jun-ichi Nishikawa: "New screening methods for chemicals with hormonal activities using interaction of nuclear hormone receptor with coactivators"Toxicology and Applied Pharmacology. 154. 76-83 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsutomu Nishihara: "Estrogenic activities of 517 chemicals by yeast two-hybrid assay"Journal of Health Science. 46. 282-298 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 西川 淳一: "内分泌かく乱物質の核内ホルモン受容体に対する影響"実験医学. 18. 731-736 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masaaki Okuno: "Dual DNA-binding specificity of PPARγ controlled by heterodimer formation with RXRα"Biochemical Journal. 353. 193-198 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masaaki Okuno: "Isolation of up-or down-regulated genes in PPARγ-expressing NIH-3T3 cells during differentiation into adipocytes"FEBS Letters. 519. 108-112 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 今川 正良: "核内受容体PPARgを介した脂肪細胞分化の分子機構"脂質栄養学. 12. 54-64 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishikawa,J., Saito,K., Goto,J., Dakeyama,F., Matsuo,M., and Nishihara,T.: "New Screening methods for chemicals with hormonal activities using interaction of nuclear hormone receptor with coactivator"Toxicol. Appl. Pharmcol.. 154(1). 76-83 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishihara,T., Nishikawa,J., Kanayama,T., Dakeyama,F., Saito,K., Imagawa,M., Takatori,S., Kitagawa,Y., Hori,S., Utsumi,H.: "Estrogenic activities of 517 chemicals by yeast two-hybrid assay"J. Health Sci.. 46(4). 282-298 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okuno,M., Arimoto,E., Ikenobu,Y., Nishihara,T., and Imagawa,M.: "Dual DNA binding specificity of peroxisome proliferator-activated receptorγ controlled heterodimer formation with retinoid X receptorα"Biochem., J.. 353(2). 193-198 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okuno,M., Arimoto,E., Nishizuka,M., Nishihara,T., and Imagawa,M.: "Isolation of up-or down-regulated genes in PPARγ-expressing NIH-3T3 cells during differentiation into adipocytes"FEBS Letters. 519(1). 108-112 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masaaki OKuno: "Isolation of up-or down-regulated genes in PPARγ-expressing NIH-3T3 cells during differentiation into adipocytes"FEBS Letters. 519・1. 108-112 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masaaki Okuno: "Dual DNA-binding specificity of peroxisome proliferator-activated receptor γ controlled by heterodimer formation with retinoid X receptor α"Biochemical Journal. 353・2. 193-198 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsutomu Nishihara: "Estrogenic activities of 517 chemicals by yeast two-hybrid assay."J.Health Sci.,. 46・4. 282-298 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 西川淳一: "内分泌撹乱物質の核内ホルモン受容体に対する影響"実験医学. 18・6. 731-736 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masaaki Okuno: "Dual DNA-binding specificity of peroxisome proliferator-activated receptor γ controlled by heterodimer formation with retinoid X receptorα."Biochem.J.,. 353・2. 193-198 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Jun-ichi Nishikawa: "New screening methods for chemicals with hormonal activities using interaction of nuclear hormone receptor with coactivators"Toxicol. Appl. Pharmacol.. 154. 76-83 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 西川淳一: "エストロゲン様物質の検出系"ファルマシア. 35・3. 241-245 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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