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Effects of environmental estrogenic pollutants on cellular functions in the noradrenergic neurons and search for their receptors

Research Project

Project/Area Number 17590111
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionUniversity of Occupational and Environmental Health

Principal Investigator

TAKAHASHI Kojiro  University of Occupational and Environmental Health, University Hospital, Director, 大学病院, 部長 (70389477)

Co-Investigator(Kenkyū-buntansha) YANAGIHARA Nobuyuki  University of Occupational and Environmental Health, School of Medicine, Professor, 医学部, 教授 (80140896)
UENO Susumu  University of Occupational and Environmental Health, School of Medicine, Assistant Professor, 医学部, 講師 (00279324)
TOYOHIRA Yumiko  University of Occupational and Environmental Health, School of Medicine, Instructor, 医学部, 助手 (90269051)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsAdrenal medullary cells / Catecholamine synthesis / Environmental estrogenic pollutants / 17β-Estradiol / Membrane estrogen receptors / MAPK / Phytoestrogens / Tyrosine hydroxylase / ダイゼイン / 副腎髄質 / レスベラトロール
Research Abstract

Environmental estrogenic pollutants are compounds that have been shown to have estrogenic effects on fetal development and reproductive systems. Less attention, however, has been paid to their influence on neuronal functions. We have examined the effects of estrogenic pollutants on catecholamine synthesis in adrenal medullary cells used as a model system of noradrenergic neurons. Treatment of cultured bovine adrenal medullary cells with p-nonylphenol and bisphenol A at 10 nM for 3 days stimulated ^<14>C-catecholamine synthesis from [^<14>C]tyrosine and tyrosine hydroxylase activity, an effect that was not inhibited by ICI 182,780, an inhibitor of estrogen receptors. Significant effects of p-nonylphenol on ^<14>C-catecholamine synthesis were observed at 0.1 nM that is 50 times lower than that of the international regulatory standard (5 nM) and the maximum effects were around at 10 nM. Short-term treatment of cells with 10 nM p-nonylphenol for 10 min also activated tyrosine hydroxylase, … More which was suppressed by U0126, an inhibitor of mitogen-activated protein kinase (MAPK) kinase. Furthermore, treatment of cells with p-nonylphenol for 5 min increased the phospho-p44/42MAPK in a concentration (1 - 1000 nM)-dependent manner.
Incubation of adrenal medullary cells with 17β-estradiol(E_2) (0.3-100 nM) or membrane-impermeable E_2-bovine serum albumin (100 nM) also acutely increased ^<14>C-catecholamine synthesis from [^<14>C]tyrosine. The plasma membrane isolated from the gland showed two classes of specific binding sites of [^3H] E_2 with apparent Kds of 3.2 and 106 nM and Bmaxs of 0.44 and 8.5 pmol/mg protein, respectively. The high-affinity binding of [^3H] E_2 was most strongly inhibited by E_2 and phytoestrogens, and to lesser extents by other steroid hormones, while it was enhanced by ICI182,780 and environmental estrogenic pollutants.
These findings suggest that E_2 and environmental estrogenic pollutants acutely stimulates catecholamine synthesis via activation of p44/42MAPK through unique estrogen receptors in the plasma membrane of bovine adrenal medulla. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (32 results)

All 2007 2006 2005

All Journal Article (29 results) Book (3 results)

  • [Journal Article] Stain treatment upregulates vascular neuronal nitric oxide synthase through Akt/NF-kB pathway2007

    • Author(s)
      Sei Nakata
    • Journal Title

      Arterioscler Thromb Vas Biol 27

      Pages: 92-98

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Stain treatment upregulates vascular neuronal nitric oxide synthase through Akt/NF-kB pathway2007

    • Author(s)
      Sei Nakata et al.
    • Journal Title

      Arterioscler Thromb Vas Biol 27

      Pages: 92-98

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Stain treatment upregulates vascular neuronal nitric oxide synthase through Akt/NF-kB pathway2007

    • Author(s)
      Sei Nakata
    • Journal Title

      Arteriscler Thromb Bas Viol 27

      Pages: 92-98

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Stimulation of catecholamine synthesis through unique estrogen receptors in the bovine adrenomedullary plasma membrane by 17β-estradiol.2006

    • Author(s)
      Nobuyuki Yanagihara
    • Journal Title

      Biochem Biophys Res Commun 339

      Pages: 548-553

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Capsaicin inhibits catecholamine secretion and synthesis by blocking Na^+ and Ca^<2+> influx through a vanilloid receptor-independent pathway in bovine adrenal medullary cells2006

    • Author(s)
      Kojiro Takahashi
    • Journal Title

      Naunyn-Schimiedeberg's Arch of Pharmacol 374

      Pages: 107-116

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Carboxyl-terminal splicing enhances physical interactions between the cytoplasmic tails of purinergic P2X receptors.2006

    • Author(s)
      Taka-aki Koshimizu
    • Journal Title

      Mol Pharmacol 69

      Pages: 1588-1598

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Stimulation of catecholamine synthesis via activation of p44/42MAPK in cultured bovine adrenal medullary cells2006

    • Author(s)
      Koji Shinkai
    • Journal Title

      Naunyn-Schimiedeberg's Arch Pharmacol (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Long-term treatment with imidapril but not with nifedipine enhances plasma NOx concentrations in patients with essential hypertension2006

    • Author(s)
      Osamu Suda
    • Journal Title

      J Pharmacol Sci 101

      Pages: 159-165

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Stimulation of catecholamine synthesis through unique estrogen receptors in the bovine adrenomedullary plasma membrane by 17β-estradiol2006

    • Author(s)
      Nobuyuki Yanagihara., et al.
    • Journal Title

      Biochem Biophys Res Commun 339

      Pages: 548-553

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Capsaicin inhibits catecholamine secretion and synthesis by blocking Na+ and Ca2+ influx through a vanilloid receptor-independent pathway in bovine adrenal medullary cells2006

    • Author(s)
      Kojiro Takahashi, et al.
    • Journal Title

      Naunyn-Schimiedeberg's Arch of Pharmacol 374

      Pages: 107-116

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Carboxyl-terminal splicing enhances physical interactions between the cytoplasmic tails of purinergic P2X receptors.2006

    • Author(s)
      Taka-aki Koshimizu et al.
    • Journal Title

      Mol Pharmacol 69

      Pages: 1588-1598

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Stimulation of catecholamine synthesis via activation of p44/42MAPK in cultured bovine adrenal medullary cells2006

    • Author(s)
      Koji Shinkai et al.
    • Journal Title

      Naunyn-Schimiedeberg's Arch Pharmacol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Long-term treatment with imidapril but not with nifedipine enhances plasma NOx concentrations in patients with essential hypertension2006

    • Author(s)
      Osamu Suda et al.
    • Journal Title

      J Pharmacol Sci 101

      Pages: 159-165

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Stimulation of catecholomine synthesis through unique estrogen receptors in the bovine adrenomedullary plasma membrane by 17β-estradiol.2006

    • Author(s)
      Nobuyuki Yanagihara
    • Journal Title

      Biochem Biophys Res Commun 339

      Pages: 548-553

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Capsaicin inhibits catecholamine secretion and synthesis by blocking Na^+ and Ca^<2+> influx through a vanilloid receptor-independent pathway in bovine adrenal medullary cells2006

    • Author(s)
      Kojiro Takahashi
    • Journal Title

      Naunyu-Schimiedeberg's Arch of Pharmacol 374

      Pages: 107-116

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Carboxyl-teminal splicing enhances physical interactions between the cytoplasmic tails of purinergic P2X receptors.2006

    • Author(s)
      Taka-aki Koshimizu
    • Journal Title

      Mol Pharmacol 69

      Pages: 1588-1598

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Stimulation of catecholamine synthesis via activation of p44/42MAPK in cultured bovine adrenal medullary cells2006

    • Author(s)
      Koji Shinkai
    • Journal Title

      Naunyu-Schimiedeberg's arch Pharmacol (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Stimulation of catecholamine synthesis by environmental estrogenic pollutants2005

    • Author(s)
      Nobuyuki Yanagihara
    • Journal Title

      Endocrinology 146

      Pages: 265-272

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Nephrogenic diabetes insipidus in mice lacking all nitric oxide synthase isoforms2005

    • Author(s)
      Tsuyoshi Morishita
    • Journal Title

      Proc Natl Acad Sci USA 102

      Pages: 10616-10621

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Vascular neuronal NO synthase is selectively upregulated by platelet-derived growth factor : Involvement of the MEK/ERK pathway2005

    • Author(s)
      Sei Nakata
    • Journal Title

      Arterioscler Thromb Vasc Biol 25

      Pages: 2502-2508

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Effects of nitric oxide synthase isoform deletion on oxytocin and vasopressin messenger RNA in mouse hypothalamus2005

    • Author(s)
      Masaya Nomura
    • Journal Title

      NeuroReport 16

      Pages: 413-417

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Intracellular cAMP controls a physical association of V-1 with CapZ in cultured mammalian endocrine cells2005

    • Author(s)
      Masashi Kitazawa
    • Journal Title

      Biochem Biophys Res Commun 331

      Pages: 181-186

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Effect of prolonged exposure to milnacipran on norepinephrine transporter in cultured bovine adrenal medullary cells2005

    • Author(s)
      Koji Shinkai
    • Journal Title

      Biochemical Pharmacology 70

      Pages: 1389-1397

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Stimulation of catecholamine synthesis by environmental estrogenic pollutants2005

    • Author(s)
      Nobuyuki Yanagihara, et al.
    • Journal Title

      Endocrinology 146

      Pages: 265-272

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nephrogenic diabetes insipidus in mice lacking all nitric oxide synthase isoforms2005

    • Author(s)
      Tsuyoshi Morishita, et al.
    • Journal Title

      Proc Natl Acad Sci USA 102

      Pages: 10616-10621

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Vascular neuronal NO synthase is selectively upregulated by platelet-derived growth factor : Involvement of the MEK/ERK pathway2005

    • Author(s)
      Sei Nakata, et al.
    • Journal Title

      Arterioscler Thromb Vasc Biol 25

      Pages: 2502-2508

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of nitric oxide synthase isoform deletion on oxytocin and vasopressin messenger RNA in mouse hypothalamus2005

    • Author(s)
      Masaya Nomura, et al.
    • Journal Title

      NeuroReport 16

      Pages: 413-417

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Intracellular cAMP controls a physical association of V-1 with CapZ in cultured mammalian endocrine cells2005

    • Author(s)
      Masashi Kitazawa, et al.
    • Journal Title

      Biochem Biophys Res Commun 331

      Pages: 181-186

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of prolonged exposure to milnacipran on norepinephrine transporter in cultured bovine adrenal medullary cells2005

    • Author(s)
      Koji Shinkai, et al.
    • Journal Title

      Biochemical Pharmacology 70

      Pages: 1389-1397

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] NOと動脈硬化(動脈硬化-最新の基礎と臨床)(中島、太崎編)2006

    • Author(s)
      筒井 正人
    • Total Pages
      314
    • Publisher
      永井書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] NOと動脈硬化(動脈硬化-最新の基礎と臨床)(中島, 太崎編)2006

    • Author(s)
      筒井 正人
    • Total Pages
      314
    • Publisher
      永井書店
    • Related Report
      2006 Annual Research Report
  • [Book] 臨床栄養学総論(小松龍史他編)2005

    • Author(s)
      柳原 延章
    • Total Pages
      245
    • Publisher
      東京化学同人
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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