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Steroid Hormones and Neuronal Survival-Molecular Biological Studies

Research Project

Project/Area Number 09044330
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research .
Research Field 内科学一般
Research InstitutionHyogo University (1998)
Showa Women's University (1997)

Principal Investigator

KITO Shozo  Research Institute of Hyogo University, Professor, 附属研究所, 教授 (00010140)

Co-Investigator(Kenkyū-buntansha) SHINGO Akiko  Research Institute of Hyogo University, Assistant Professor, 附属研究所, 講師 (50309499)
BIGGIO G.  University of Cagliari, Department of Experimental Biology, Professor, Department of Exp, 教授
BARNARD E.A.  Cambridge University, Department of Pharmacology, Professor, 教授
OLSEN R.W.  UCLA School of Medicine, Department of Pharmacology, Professor, 教授
TOHYAMA Masaya  Osaka University, School of Medicine, Professor, 医学部, 教授 (40028593)
BARNARD E.A  Camoridge University Department of Pharm, 教授
OLSEN R.W  UCLA School of Medicine, 教授
OLSEN R W  UCLA School of Medicine, 教授
野村 靖幸  北海道大学, 薬学部, 教授 (00034041)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥3,300,000 (Direct Cost: ¥3,300,000)
Keywordsestrogen / IGF-1 mRNA / c-fos mRNA / AP-1 DNA binding activities / CREB DNA binding activities / Ca ion / nifedipine / tamoxifen / IGF-1 mRNA / c-fos mRNA / estrogen / IGF・1〜RNA / 海馬 / 大脳皮質 / GAP43〜RNA / カイニン酸 / Ca拮抗薬
Research Abstract

In our foregoing studies, we found that estrogen increased the survival rate of cultured rat hippocampal neurons. Then, we confirmed that a general injection of 0.5mg/kg beta-estradiol induced IGF-1 mRNA expression in the rat cerebral cortex as well as hippocampus.
Motivated by these facts, we have been trying to pursuit the signal transduction passway through which estrogen induces IGF-1 mRNA expression, and have so far obtained the following results.
1. Estrogen caused a transient increase of intracellular Ca ion concentration in some population of cultured rat hippocampal neurons. This increase was inhibited by nifedipine.
2. A general injection of 0.5mg/kg beta-estradiol Induced c-fos mRNA expression reaching the maximum at 3OmIn after the injection in the rat cerebral cortex and hippocampus.
3. A subcutaneous injection of 0.5mg/kg beta-estradiol potentiated the AP-1 DNA binding activities in both hippocampus and cerebral cortex reaching the maximum at 120min.
4. A subcutaneous injectio … More n of 0.5mg/kg beta-estradiol increased the CREB (cyclic AMP response element binding protein) DNA binding activities in both cerebral cortex and hippocampus. The increase started at 45mm after the injection and the binding was continuously incremental up to 120min in the hippocampus. In the cerebral cortex, the increase of the CREB DNA binding activities was transient.
5. When observed by RNase protection assay in the rat hippocarnpus, estrogen-induced IGF-1 mRNA expression was blocked by a previous injection of nifedipine, but not inhibited by tamoxifen, a nuclear estrogen receptor partial antagonist.
6. Recently, it is advocated that there are estrogen specific binding sites not only in the nucleus but also on the cell membrane in which they are conjugated with G protein in relation with cyclic AMP.in our experiments, it was shown that in the hlppocarnpus, estrogen caused an upregulation of estrogen receptor alpha which was inhibited by nicotine . These phenomena were due to the complicated crosstalk among the newly-discovered membranous estrogen binding site, classical nuclear estrogen receptor and nicotinic receptor.
Summarizing these results, it was concluded that estrogen-induced cyclic AMP-dependant intraneuronal Ca ion concentration caused increase of CREB DNA binding activity, induction of c-fos mRNA expression and then increase of AP-1 DNA binding activIties in succession, and finally brought about induction of IGF-1 mRNA expression. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (45 results)

All Other

All Publications (45 results)

  • [Publications] 鬼頭昭三: "Neuronにおけるnicotine-estrogen機能相関に関する研究" 平成10年度喫煙科学研究財団研究年報. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.S.Shingo: "Estrogen works as a repair system in brain by inducing IGF-1 mRNA." The Japanese Journal of Pharmacology.Vol.76 Supplement1. 190 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Kito: "Nicotine and estrogen crosstalk in the brain as to IGF-1 mRNA expression." The Japanese Jornal of Pharmacology.Vol.76 Supplement1. 190 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.S.Shingo: "Mechanisms of estrogen action as repair system in brain." 28th Annual Meeting Society for Neuroscience. Vol.24 No.2. 511.6 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Kito: "Nicotine-estrogen crosstalk in brain with regard to CREB binding activities and IGF-1 mRNA expression." 28th Annual Meeting Society for Neuroscience. Vol.24 No.2. 511.5 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 新郷明子: "脳神経系とインスリン様成長因子" 日本農芸化学会誌. Vol.72 NO.2. 175-179 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 新郷明子: "脳内IGF-1mRNA発現とニコチン-エストロゲン機能相関" 医学と生物学. 137(5). 167-172 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 鬼頭昭三: "Neuronにおけるnicotine-estrogen機能相関に関する研究" 平成9年度喫煙科学研究財団研究年報. 620-625 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Tohyama: "Increased transcription of glutamate-aspartate transporter (GLAST/GluT-1) mRNA following kainic acid-induced limbic seizure." Malecular Brain Research. 55. 54-60 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] G.Biggo: "Stress and neurosteroids in adult and aged rats." Experimental Gerontology. Vol.33, Nos.7/8. 697-712 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.S.Shingo: "Estrogen effects on the kainic acid-injured brain." The Japanese Journal of Pharmacology. Vol.73 SupplementI. 524 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 新郷明子: "ゲルシフトアッセイからみたエストロゲンとニコチンのクロストーク" 医学と生物学. 134(1). 3-7 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Kito: "Nicotine and estrogen cross talk in brain in IGF-1 mRNA expression." 27th Annual Meeting Society for Neuroscience. Vol.23 No.2. 670.11 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.S.Shingo: "Estrogen as a repair system in brain by inducing IGF-1 mRNA." 27th Annual Meeting Society for Neuroscience. Vol.23 No.2. 670.12 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.H.Joh: "Structure/Function relationship of the cAMP response element in tyrosine hydroxylase gene transcription." The Journal of Biological Chemistry. Vol.272 No.31, Aug 1. 19158-19164 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Tohyama: "Characterization of glycine release mediated by glycine transporter 1 stably expressed in HEK-293 cells." Molecular Brain Research. 49. 89-94 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 鬼頭昭三: "Neuronにおけるnicotine-estrogen機能相関に関する研究" 平成8年度喫煙科学研究財団研究年報. 628-632 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Kito: "Estrogen-nicotine crosstalk in rat brain" Smoking Research Foundation Annual Research Report. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.S.Shingo: "Estrogen works as a repair system in brain by inducing IGF-1 mRNA" The Japanese Journal of Pharmacology. Vol.76, Supplement I. 190 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Kito: "Nicotine and estrogen crosstalk in brain as to IGF-1 mRNA expression" The Japanese Journal of Pharmacology. Vol.76, Supplement I. 190 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.S.Shingo: "Mechanisms of estrogen action as repair system in brain" 28th Annual Meeting Society for Neuroscience. Vol.24 No.2. 511.6 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Kito: "Nicotine-estrogen crosstalk in brain with regard to CREB binding activities and IGF-1 mRNA expression" 28th Annual Meeting Society for Neuroscience. Vol.24 No.2. 511.5 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.S.Shingo: "Functional significance of insulin-like growth factor in brain." Nippon Nogeikagaku Kaishi. Vol 72, No.2. 175-179 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.S.Shingo: "Nicotine-estrogen interaction in intra-neuronal expression of IGF-1 mRNA" Medicine and Biology. 137 (5). 167-172 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Kito: "Estrogen works as a repair system in brain by inducing IGF-1 mRNA" Smoking Research Foundation Annual Research Report. 620-625 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Tohyama: "Increased transcription of glutamate-aspartate transporter (GLAST/GluT-1) mRNA following kainic acid-induced limbic seizure" Molecular Brain Research. 55. 54-60 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] G.Biggio: "Stress and neurosteroids in adult and aged rats" Experimental Gerontology. Vol.33., Nos.7/8. 697-712 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.S.Shingo: "Estrogen effects on a kainic acid-injured brain" The Japanese Journal of Pharmacology. Vol.73 Supplement I. 524 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.S.Shingo: "Estrogen-nicotine cross-talk in rat brain" Medicine and Biology. 134 (1). 3-7 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Kito: "Nicotine and estrogen cross talk in brain in IGF-1mRNA expression" 27th Annual Meeting Society for Neuroscience. Vol.23 No.2. 670.11 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.S.Shingo: "Estrogen as a repair system in brain by inducing IGF-1mRNA" 27th Annual Meeting Society for Neuroscience. Vol.23 No.2. 670.12 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.H.Joh: "Structure/Function relationship of the cAMP response element in tyrosine hydroxylase gene transcription" The Journal of Biological Chemistry. Vol.272, No.31. 19158-19164 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Tohyama: "Characterization of glycine release mediated by glycine transporter 1 stably expressed in HEK-293 cells" Molecular Brain Research. 49. 89-94 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Kito: "Estrogen Works as a repair system in brain by inducing IGF-1 mRNA" Smoking Research Foundation Annual Research Report. 628-632 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.S.Shingo: "Estrogen works as a repair system in brain by inducing IGF-1 mRNA." The Japanese Journal of Pharmacology. Vol.76 Supplement1. 190 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Kito: "Nicotine and estrogen crosstalk in brain as to IGF-1 mRNA" The Japanese Journal of Pharmacology. Vol.76 Supplement1. 190 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] A.S.Shingo: "Mechanisms of estrogen action as repair system in brain." 28th Annual Meeting Society for Neuroscience. Vol.24 No.2. 511.6 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Kito: "Nicotine-estrogen crosstalk in brain with regard to CREB binding activities and IGF-1 mRNA expression." 28th Annual Meeting Society for Neuroscience. Vol.24 No.2. 511.5 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 新郷明子: "脳内IGF-1 mRNA発現とニコチン-エストロゲン機能相関" 医学と生物学. 137(5). 167-172 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 鬼頭昭三: "Neuronにおけるnicotine-estrogen機能相関に関する研究" 平成9年度喫煙科学研究財団研究年報. 620-625 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] A.S.Shingo: "Estrogen effects on a kainic acid-injured brain." The Japanese Journal of Pharma cology. Vol.73 Supplement I. 524 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 鬼頭 昭三: "Neuronにおけるnicotine-estrogen機能相関に関する研究" 平成8年度喫煙科学研究財団研究年報. 628-632 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] A.S.Shingo: "Estrogen is as a repair system in brain by inducing IGF-1mRNA" 27th Annual Meeting Society for Neuroscience. Vol.23 No.2. 670.12 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Kito: "Nicotine and estrogen cross talk in brain in IGF-1 mRNA expression." 27th Annual Meeting Society for Neuroscience. Vol.23 No.2. 670.11 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 新郷 明子: "脳神経系とインスリン様成長因子" 日本農芸化学会誌. Vol.72 No.2. 175-179 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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