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Effects of exogenous endocrine-disrupters on the brain regions related to sexual differentiation and aggressive behavior

Research Project

Project/Area Number 12836010
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research InstitutionYamaguchi University

Principal Investigator

SHINODA Koh  Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (40192108)

Co-Investigator(Kenkyū-buntansha) KAWATA Keisuke  Yamaguchi University, School of Medicine, Instructor, 医学部, 助手 (20284242)
HOBARA Tatsuya  Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (10116501)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordsoctylphenol / nonylphenol / endocrine disrupter / sexual differentiation / estrogen receptor / androgen receptor / brain / sex steroid / アロマテース / 内側視索前野 / 内側扁桃体 / 分界条床核 / ビスフェノールA
Research Abstract

Effects of endogenous sex-hormones and exogenous alkylphenolic compounds on expression of intracranial estrogen- and androgen-receptor (EsR and AnR) have immunohistochemically been evaluated in the rat medial preoptic nucleus (MPN), principal nucleus of the bed nucleus of the stria terminalis (prBST), posterodorsal part of the medial amygdaloid nucleus (pdMAmg), which have been considered to be related to sexual functions and aggressive behavior. Numbers of the EsRs and AnRs were counted in castrated rats which were injected vehicle-oil (control), 17β-estradiol (E2), dihydrotestosterone (DHT), testosterone (T), nonylphenol (NP) or p-tert-octylphenol (OP). In controls, expression of brain EsRs was strongly enhanced, while that of AnRs was almost completely suppressed in almost all brain regions. Administration of higher dose of E2 (100〜250 μg/100g for 1 week) resulted in prominent decrease of the number of EsR and moderate increase of that of AnR in the prBST and pdMAmg and less increas … More e and decrease in the MPN. Administration of DHT (100〜250 μg/100g 1 week) resulted in prominent increase of that of AnR and slight decrease of the number of EsR in all three regions. Administration of lower dose of T (100〜250 μg/100g for 1 week) resulted in prominent decrease of the number of EsR specifically in the prBST and pdMAmg and far less decrease in the MPN, but not successfully increase that of AnR, in any of the three regions. Administration of higher dose of T (1mg/100g for 1 week) prominently increased the number of the AnR in addition to prominent decrease of EsR have and moderate increase of that of AnR in all three regions. Injection of NP (40mg/100g for 3 days) or OP (40mg/100g for 3 days) was found to show estrogenic EsR-down regulation effects in all three brain regions as seen in the case of administration of lower dose of E2 (10〜25 μg/100g for 3 days), which resulted in moderate decrease of the number of EsR in the prBST and pdMAmg and less decrease in the MPN. Taken together, the present study strongly suggested that endogenous sex-hormone and exogenous alkylphenolic compounds effect on brain sexual organization and activation through up- or down-regulation of intracranial EsR or AnR expression in addition to direct actions on the two receptors. Thus it might be possible that endocrine-disrupters such as NP or OP can interfere sexual differentiation and regulation of the sexual functions and aggressive behavior through their estrogenic down-regulation effects on EsR in the MPN, prBST and pdMAmg. Less

Report

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

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Koumei Takeda: "WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain"Human Molecular Genetics. 10. 477-484 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 篠田 晃: "神経組織における電子顕微鏡を用いた免疫組織化学-プレエンベッディング法-"組織細胞科学2001. 117-122 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeda,K. et al.: "WFS1 gene product: predominant subcellular localixation to endoplasmic reticulum in cultured cells and neuronal expression in the rat brain"Hum Mol Genet. 10. 477-484 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinoda,K.: "Pre-embedding immuno-electron microscopic in the nervous tissues"Histochemistry and Cytochemistry 2001. 117-122 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koumei Takeda: "WFS1 (Wolfram syndrome1) gene product : predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain"Human Molecular Genetics. 10・5. 477-484 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 篠田晃: "神経組織における電子顕微鏡を用いた免疫組織化学-プレエンベッディング法-"組織細胞科学2001. 117-122 (2001)

    • Related Report
      2001 Annual Research Report

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

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