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Non-estrogenic effects of endocrine disrupters on the central nervous system

Research Project

Project/Area Number 14570062
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology (including Physical medicine and Nutritional physiology)
Research InstitutionYokohama City University Graduate School of Medicine

Principal Investigator

FUNABASHI Toshiya  Yokohama City University Graduate School of Medicine, Department of Neuroendocrinology, Associate Professor, 大学院・医学研究科, 助教授 (70229102)

Co-Investigator(Kenkyū-buntansha) MITSUSHIMA Dai  Yokohama City University Graduate School of Medicine, Department of Neuroendocrinology, Assistant Professor, 大学院・医学研究科, 講師 (70264603)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsEndocrine disrupter / Cerebral cortex / Hippocampus / Bisphenol A / Octylphenol / Nonylphenol / Progesterone receptor / Estrogen / 中枢神経系 / ラット / 新皮質 / 前頭葉
Research Abstract

Alkylphenols, such as p-nonylphenol (NP) and 4-tert-octylphenol (OP), and bisphenol A (BPA) are called endocrine disrupters. We examined whether these endocrine disrupters affected progesterone receptor (PR) mRNA in the adult female rat neocortex. In one experiment, ovariectomized rats were given a subcutaneous injection of 10 mg of NP, 10 mg of OP, or 10 mg of BPA, or sesame oil alone as control. Twenty-four h after the injection, the frontal cortex, parietal cortex, and temporal cortex was collected. In a second experiment to study the time-course of the effects of BPA on PR mRNA, the ovariectomized rats were given a subcutaneous injection of 10 mg of BPA and killed 0, 6, 12, and 24 h after the injection. In addition to the frontal cortex and temporal cortex, the occipital cortex and hippocampus were also collected. Northern blotting revealed that, in the first experiment, injection of NP, OP, or BPA significantly increased PR mRNA in the frontal cortex without affecting PR mRNA in the parietal cortex. In the temporal cortex, BPA significantly decreased PR mRNA, but both NP and OP did not produce significant changes. The second experiment revealed that, injection. In the temporal cortex, PR mRNA was significantly decreased 6 h after the injection of BPA and was still significantly low 24 h after the injection. In the hippocampus, BPA induced a significant increase in PR mRNA only at 24 h after the injection. No significant change was observed in the occipital cortex. These results suggest that, even in adult rats, endocrine disrupters alter the neocortical function by affecting the PR system, although the physiological significance of PR in the affected area is not known.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Kawaguchi M, Funabashi T, Aiba S, Kimura F: "Butyl benzyl phthalate, an endocrine disrupter, inhibits pulsatile luteinizing hormone secretion under an insulin-induced hypoglycaemic state in ovariectomized rats"Journal of Neuroendocrinology. 14. 486-491 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funabashi T, Daikoku S, Suyama K, Mitsushima D, Sano A, Kimura F: "Role of gamma-aminobutyric acid neurons in the release of gonadotropin-releasing hormone in cultured rat embryonic olfactory placodes"Neuroendocrinology. 76. 193-202 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funabashi T, Sano A, Mitsushima D, Kimura F: "Bisphenol A increases progesterone receptor immunoreactivity in the hypothalamus in a dose-dependent manner and affects sexual behaviour in adult ovariectomized rats"Journal of Neuroendocrinology. 15. 134-140 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mitsushima D, Funabashi T, Kimura F: "Estrogen increases messenger RNA and immunoreactivity of aryl-hydrocarbon receptor nuclear translocator 2 in the rat mediobasal hypothalamus"Biochemical and Biophysical Research Communications. 307. 248-253 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funabashi T, Mitsushima D, Nakamura TJ, Uemura T, Hirahara F, Shinohara K, Suyama K, Kimura F: "Gonadotropin-releasing hormone (GnRH) surge generator in female rats"Progress in Brain Research (Review). 141. 165-173 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funabashi T, Nakamura TJ, Kimura F: "p-Nonylphenol, 4-tert-octylphenol and bisphenol A increase the expression of progesterone receptor mRNA in the frontal cortex of adult ovariectomized rats"Journal of Neuroendocrinology. 16. 99-104 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funabashi T, Kawaguchi M, Furuta M, Fukushima A, Kimura F: "Exposure to bisphenol A during gestation and lactation causes loss of sex difference in corticotropin-releasing hormone-immunoreactive neurons in the bed nucleus of the stria terminalis of rats"Psychoneuroendocrinology. 29. 475-485 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 貴邑冨久子, 舩橋利也: "内分泌攪乱物質の中枢作用-Progesterone受容体発現に及ぼすbisphenol Aの影響を指標として-"脳の科学. 25. 1125-1131 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 舩橋利也, 貴邑冨久子: "ラットにおけるGnRHサージジェネレータの神経機構"神経研究の進歩. 47. 389-397 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 舩橋利也, 貴邑冨久子: "内分泌攪乱物質の中枢神経系への影響"医事新報. 4137. 17-20 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawaguchi M, Funabashi T, Aiba S, Kimura F: "Butyl benzyl phthalate, an endocrine disrupter, inhibits pulsatile luteinizing hormone secretion under an insulin-induced hypoglycaemic state in ovariectomized rats."J Neuroendocrinol. 14. 486-491 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funabashi T, Daikoku S, Suyama K, Mitsushima D, Sano A, Kimura F: "Role of gamma-aminobutyric acid neurons in the release of gonadotropin-releasing hormone in cultured rat embryonic olfactory placodes."Neuroendocrinology. 76. 193-202 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funabashi T, Sano A, Mitsushima D, Kimura F: "Bisphenol A increases progesterone receptor immunoreactivity in the hypothalamus in a dose-dependent manner and affects sexual behaviour in adult ovariectomized rats."J Neuroendocrinol. 15. 134-140 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mitsushima D, Funabashi T, Kimura F: "Estrogen increases messenger RNA and immunoreactivity of aryl-hydrocarbon receptor nuclear translocator 2 in the rat mediobasal hypothalamus."Biochem Biophys Res Commun. 307. 248-253 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funabashi T, Mitsushima D, Nakamura TJ, Uemura T, Hirahara F, Shinohara K, Suyama K, Kimura F: "Gonadotropin-releasing hormone (GnRH) surge generator in female rats."Prog Brain Res. 141. 165-173 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funabashi T, Kawaguchi M, Furuta M, Fukushima A, Kimura F: "Exposure to bisphenol A during gestation and lactation causes loss of sex difference in corticotropin-releasing hormone-immunoreactive neurons in the bed nucleus of the stria terminalis of rats."Psychoneuroendocrinology. 29. 475-485 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funabashi T, Nakamura TJ, Kimura F: "p-Nonylphenol, 4-tert-octylphenol and bisphenol A increase the expression of progesterone receptor mRNA in the frontal cortex of adult ovariectomized rats."J Neuroendocrinol.. 16. 99-104 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Funabashi T, et al.: "p-Nonylphenol, 4-tert-octylphenol and bisphenol A increase the expression of progesterone receptor mRNA in the frontal cortex of adult ovariectomized rats"Journal of Neuroendocrinology. 16. 99-104 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 貴邑冨久子, 他: "内分泌撹乱物質の中枢作用-Progesterone受容体発現に及ぼすbisphenol Aの影響を指標として-"脳の科学. 25. 1125-1131 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 舩橋利也, 他: "ラットにおけるGnRHサージジェネレーターの神経機構"神経研究の進歩. 47. 389-397 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 舩橋利也, 他: "内分泌撹乱物質の中枢神経系への影響-ビスフェノールAを例として-"医事新報. 4137. 17-20 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Funabashi T, Shinohara K, Kimura F: "Neuronal control circuit for the gonadotropin-releasing hormone surge in rats"Neuroplasticity, development, and steroid hormone action. 169-176 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Funabashi T, et al.: "Gonadotropin-releasing hormone (GnRH) surge generator in female rats"Progress in Brain Research. 141. 165-173 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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