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Effects of Environmental Chemicals on Bone Metabolism through Steroid and Xenobiotic Receptor (SXR)

Research Project

Project/Area Number 22591020
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research Institution公益財団法人冲中記念成人病研究所 (2012)
Okinaka Memorial Institute for Medical Research (2010-2011)

Principal Investigator

TAKESHITA Akira  公益財団法人冲中記念成人病研究所, 研究員 (20322646)

Co-Investigator(Kenkyū-buntansha) TAKEUCHI Yasuhiro  冲中記念成人病研究所, 主任研究員 (50202164)
Co-Investigator(Renkei-kenkyūsha) KOIBUCHI Noriyuki  群馬大学, 医学研究科, 教授 (80234681)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords内分泌学 / SXR / 薬剤性骨軟化症 / 環境化学物質 / CYP3A4 / アセチルトリブチルクエン酸 / ビスフェノールA / フタル酸化合物 / TRPV6
Research Abstract

Steroid and xenobiotic receptor (SXR) is activated by endogenous and exogenous chemicals. SXR is highly expressed in the liver and intestine, where it regulates CYP3A4, which in turn controls xenobiotic and endogenous hormone metabolism including active vitamin D. However, it is unclear whether drug additives exert such activity. We found that four of eight drug additives increased SXR-mediated transcription. In particular, acetyl tributyl citrate (ATBC), an industrial plasticizer widely used in products such as food wrap, vinyl toys, and pharmaceutical excipients, strongly activated SXR. Our in vitro and in vivo results suggest that ATBC specifically induces CYP3A in the intestine by activating SXR. We suggest that ATBC-containing products be used cautiously because they may alter metabolism of vitamin D.

Report

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

    (14 results)

All 2013 2012 2011

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (9 results)

  • [Journal Article] Mitotane induces CYP3A4 expression via activation of the steroid and xenobiotic receptor2013

    • Author(s)
      Akira Takeshita, Junko Igarashi-Migitaka, Noriyuki Koibuchi, Yasuhiro Takeuchi.
    • Journal Title

      Journal of Endocrinology

      Volume: Vol.216 Issue: 3 Pages: 297-305

    • DOI

      10.1530/joe-12-0297

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interaction of silencing mediator for retinoid an d thyroid receptors with steroid and xenobiotic receptor on multidrug resi stance 1 promoter2013

    • Author(s)
      Kazumi Hirooka-Masui, Ronny Lesmana, Toshiharu Iwasaki, Ming X, Kaori Hay asaka, Mizuki Haraguchi, Akira Takesh ita, Noriaki Shimokawa, Koujirou Yama moto, Noriyuki Koibuchi
    • Journal Title

      Life Sciences

      Volume: Vol.92 Pages: 911-915

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interaction of silencing mediator for retinoid and thyroid receptors with steroid and xenobiotic receptor on multidrug resistance 1 promoter2013

    • Author(s)
      Kazumi Hirooka-Masui
    • Journal Title

      Life Sciences

      Volume: 92 Issue: 17-19 Pages: 911-915

    • DOI

      10.1016/j.lfs.2013.03.007

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hidden culprit of primary hyperparathyroidism2012

    • Author(s)
      Naoka Murakami
    • Journal Title

      Journal of Clinical Endocrinology and Metabolism

      Volume: 97 Issue: 10 Pages: 3410-3411

    • DOI

      10.1210/jc.2012-2190

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acetyl tributyl citrate, the most widely used phthalate substitute plasticizer, induces cytochrome p450 3A through steroid and xenobiotic receptor2011

    • Author(s)
      Akira Takeshita, Junko Igarashi-Migitaka, Kazusa Nishiyama, Hideyo Takahashi, Yasuhiro Takeuchi, and Noriyuki Koibuchi
    • Journal Title

      Toxicological Sciences

      Volume: Vol.123 Issue: 2 Pages: 460-470

    • DOI

      10.1093/toxsci/kfr178

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] ラットvivoモデルを用いた、骨吸収抑制剤がビタミンD代謝に及ぼす影響の検討.厚生労働科学研究費補助金(難治疾患克服研究事業)ホルモン受容機構異常に関する調査研究2013

    • Author(s)
      竹下章、竹内靖博
    • Organizer
      平成24年度研究報告会
    • Place of Presentation
      霞ヶ関コモンゲート西館
    • Year and Date
      2013-01-25
    • Related Report
      2012 Final Research Report
  • [Presentation] ラットvivoモデルを用いた、骨吸収抑制剤がビタミンD代謝に及ぼす影響の検討2013

    • Author(s)
      竹下章、五十嵐潤子、鯉淵典之、竹内靖博
    • Organizer
      第86回日本内分泌学会学術総会
    • Place of Presentation
      仙台国際センター
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] ラットvivoモデルを用いた、骨吸収抑制剤がビタミンD代謝に及ぼす影響の検討2013

    • Author(s)
      竹下章
    • Organizer
      厚生労働科学研究費補助金(難治疾患克服研究事業)ホルモン受容機構異常に関する調査研究  平成23年度研究報告会
    • Place of Presentation
      霞ヶ関コモンゲート西館
    • Related Report
      2012 Annual Research Report
  • [Presentation] 薬剤による肝・腸管におけるビタミンD関連遺伝子発現の制御機構:薬剤性骨軟化症の病態との関連について.厚生労働科学研究費補助金(難治疾患克服研究事業)ホルモン受容機構異常に関する調査研究2012

    • Author(s)
      竹下章、竹内靖博
    • Organizer
      平成23年度研究報告会
    • Place of Presentation
      霞ヶ関コモンゲート西館
    • Year and Date
      2012-01-13
    • Related Report
      2012 Final Research Report
  • [Presentation] 薬剤による肝・腸管におけるビタミンD関連遺伝子発現の制御機構:薬剤性骨軟化症の病態との関連について2012

    • Author(s)
      竹下章、竹内靖博
    • Organizer
      厚生労働科学研究費補助金(難治疾患克服研究事業)ホルモン受容機構異常に関する調査研究平成23年度研究報告会
    • Place of Presentation
      霞ヶ関コモンゲート西館
    • Year and Date
      2012-01-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] SXRとVDRのクロストークが薬剤性骨軟化症の成因に関与する2012

    • Author(s)
      竹下章、鯉淵典之、竹内靖博
    • Organizer
      第85回日本内分泌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] 薬剤添加物によるステロイドゼノバイオティック受容体SXRを介した腸管特異的なCYP3A4の酵素誘導2011

    • Author(s)
      竹下章、五十嵐潤子、西山和沙、高橋秀依、鯉淵典之、竹内靖博
    • Organizer
      第84回日本内分泌学会学術総会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2011-04-21
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] 環境化学物質が骨代謝障害を惹起する可能性の検討.厚生労働科学研究費補助金(難治疾患克服研究事業)ホルモン受容機構異常に関する調査研究2011

    • Author(s)
      竹下章、鈴木尚宜、竹内靖博
    • Organizer
      平成22年度研究報告会
    • Place of Presentation
      霞ヶ関コモンゲート西館
    • Year and Date
      2011-01-14
    • Related Report
      2012 Final Research Report
  • [Presentation] 環境化学物質が骨代謝障害を惹起する可能性の検討2011

    • Author(s)
      竹下章、鈴木尚宜、竹内靖博
    • Organizer
      厚生労働科学研究費補助金(難治疾患克服研究事業)ホルモン受容機構異常に関する調査研究平成22年度研究報告会
    • Place of Presentation
      霞ヶ関コモンゲート西館
    • Year and Date
      2011-01-14
    • Related Report
      2010 Annual Research Report

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Published: 2010-11-30   Modified: 2019-07-29  

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