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Tne investigation for novel metabolic pathway of steroids and xenobiotics

Research Project

Project/Area Number 12671601
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionOkayama University

Principal Investigator

MASUYAMA Hisashi  Okayama University, Hospital, Assistant, 医学部・附属病院, 助手 (30314678)

Co-Investigator(Kenkyū-buntansha) MIZUTANI Yasushi  Okayama University, Hospital, Assistant, 医学部・附属病院, 助手 (20294465)
HIRAMATSU Yuji  Okayama Univereity, Graduate School of Medicine and Dentistry, Associate Professor, 大学院・医歯学総合研究科, 助教授 (80218817)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordspregnane X receptor / cytochrome P450 / steroidogenesis / nuclear receptor / xenobiotics / degradation / SUG1 / 核内レセプター
Research Abstract

Recently, Pregnane X receptor (PXR), a new member of the nuclear receptor superfamily, was shown to mediate the effects of several steroid hormones and xenobiotics on cytochrome P450 3A genes (CYP3A), suggesting that PXR may play a role in steroid hormone metabolism. Here, we demonstrated that phthalic acid and nonylphenol, endocrine disrupting chemicals (EDCs), stimulated PXR- mediated transcription and that PXR interacted with two nuclear receptor coactivator proteins, steroid hormone receptor coactivator-1 and receptor interacting protein 140, in the presence of phthalic acid or nonylphenol. The expression of PXR mRNA was observed in the liver, intestine, uterus, ovary and placenta. The expressions in the liver and ovary increased toward term about fifty-fold compared to that of non-pregnancy and decreased postpartum. Its expression in the placenta was not drastically changed toward term. CYP3A was also expressed in the liver, ovary, and placenta. The expressions of CYP3A mRNA as well as PXR in the liver and ovary increased about twenty-fold during prenatal period. Finally, we demonstrated that pregnane X receptor (PXR) interacted with suppressor for gall (SUGI), a component of the 26S proteasome, in a progesterone-dependent manner, but that phthalic acid and nonylphehol, which activated PXR-mediated transcription, did not enhance this interaction. Moreover, these EDC blocked the PXR degradation by proteasome.
These data suggest that EDCs may affect endocrine functions by altering steroid hormone metabolism through PXR and that EDCs may also affect PXR-mediated transcription of target genes through the upregulation of PXR protein level. And PXR may play certain roles in perinatal period, possibly in the protection of the feto-maternal system from the toxic effect of endogenous steroids and foreign substrates.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] H.Masuyama, Y.Hiramatsu, T.Kudo, et al.: "Endocrine Disrupting Chemicals Phthalic Acid and Nonylphenol Activate Pregnane X Receotor-mediated Transcription"Molecular Endocrinology. 14. 421-428 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Hiramatsu, H.Masuyama, T.Kudo, et al.: "Streptozotocin-induced Diabetic Pregnant Rats Exhibit the Signs and Symptoms Mimicking Preeclampsia"Metabolism. 49. 853-857 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 増山 寿, 工藤尚文: "新しい核内受容体であるPregnane X receptorの妊娠中及び内分泌攪乱作用における役割"生活と環境. 46. 43-48 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Masuyama, Y.Hiramatsu, T.Kudo, et al.: "The Expression of pregnane X receptor and its target gene, cytochrome P450 3A1, in Perinatal Mouse"Molecular and Cellular Endocrinology. 172. 47-56 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 増山 寿, 平松祐司, 工藤尚文: "プロゲステロン-最近の話題 新しい核内受容体Pregnane X Receptor(PXR)"Hormone Frontier in Gynecology. 8. 365-372 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hisashi Masuyama, Hideshi Inoshita, Yuji Hiramatsu, Takafumi Kudo: "Ligands have various potential effects on the degradation of pregnane X receptor by proteasome"Endocrinology. 143. 55-61 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Masayama, Y. Hiramatsu, M . Kunitomi, T. Kudo, P.N. MacDonald: "Endocrine Disrupting Chemicals Phthalic Acid and Nonylphenol Activate Pregnane X Receptor-mediated Transcription."Mol Endocrinol. 14. 421-428 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Hiramatsu, H. Masuyama, Y. Mizutani, T. Kudo, N. Oguni, Y. Oguni: "How to Reduce the Delivery of Heavy-For-Dates Infants ; Their Backgrounds and Relationship with Gestational Diabetes."J Obstet Gynecol Res. 26. 193-198 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] G. Ishihara, Y. Hiramatsu, H. Masuyama, T. Kudo: "Streptozotocin-induced Diabetic Pregnant Rats Exhibit the Signs and Symptoms Mimicking Preeclampsia."Metabolism. 49. 853-857 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Masuyama, Y. Hiramatsu, Y. Mizutani, H Inoshita,T. Kudo: "The Expression of pregnane X receptor and its target gene, cytochrome P450 3A1, in Perinatal Mouse."Mol Cell Endocrinol. 172. 47-56 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Mimura, M. Kishida, H. Masuyama, N. Suwaki, J. Kodama, F. Otsuka, H. Kataoka, T. Yamauchi, T. Ogura, T. Kudo, H. Makino: "Coexistence of Graves' disease and Struma Ovari i: Case Report and literatureReview."Endocrine J. 48. 255-260 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hisashi Masuyama, Hideshi Inoshita, Yuji Hiramatsu, Takafumi Kudo: "Ligands have various potential effects on the degradation of pregnane X receptor by proteasome."Endocrinology. 143. 55-61 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Masuyama, Y.Hiramatsu, T.Kudo, et al.: "Endocrine Disrupting Chemicals Phthalic Acid and Nonylphenol Activate Pregnane X Receptor-mediated Transcription"Molecular Endocrinology. 14. 421-428 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Hiramatsu, H.Masuyama, T.Kudo, et al.: "Streptozotocin-induced Diabetic Pregnant Rats Exhibit the Signs and Symptoms Mimicking Preeclampsia"Metabolism. 49. 853-857 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 増山 寿, 工藤尚文: "新しい核内受容体であるPregnane X rcceptorの妊娠中及び内分泌攪乱作用における役割"生活と環境. 46. 43-48 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Masuyama, Y.Hiramatsu, T.Kudo, et al.: "The Expression of pregnane X receptor and its target gene, cytochrome P450 3A1, in Perinatal Mouse"Molecular and Cellular Endocrinology. 172. 47-56 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 増山 寿, 平松祐司, 工藤尚文: "プロゲステロン-最近の話題-新しい核内受容体Pregnane X Receptor(PXR)"Hormone Frontier in Gynecology. 8. 365-372 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hisashi Masuyama, Hideshi Inoshita, Yuji Hiramatsu, Takafumi Kudo: "Ligands have various potential effects on the degradation of pregnane X receptor by proteasome"Endocrinology. 143. 55-61 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Masuyama,Y.Hiramatsu,T.Kudo, et al: "Endocrine Disrupting Chemicals Phthalic Acid and Nonylphenol Activate Pregnane X Receptor-mediated Transcription"Molecular Endocrinology. 14. 421-428 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Hiramatsu,H.Masuyama,T.Kudo, et al: "Streptozotocin-induced Diabetic Pregnant Rats Exhibit the Signs and Symptoms Mimicking Preeclampsia"Metabolism. 49. 853-857 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 増山寿,水谷靖司,平松祐司 他: "新しいステロイド,Xenobiotics代謝調節機構の解明"産婦人科の治療. 82. 103 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Masuyama,Y.Hiramatsu,T.Kudo, et al: "The Expression of pregnane X receptor and its target gene, cytochrome P450 3A1, in Perinatal Mouse"Molecular and Cellular Endocrinology. 172. 47-56 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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