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Endocrinological analysis of genetically modified mice with abnormal estrogen metablism

Research Project

Project/Area Number 16590916
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionFujita Health University

Principal Investigator

HARADA Nobuhiro  Fujita Health University, School of Medicine, Professor, 医学部, 教授 (00189705)

Co-Investigator(Kenkyū-buntansha) HONDA Shin-ichiro  Fujita Health University, School of Medicine, Lecturer, 医学部, 講師 (40257639)
SASAKI Emi  Fujita Health University, School of Medicine, Assistant, 医学部, 助手 (20178635)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsTransgenic mouse / Knockout mouse / Estrogen / Aromatase / Steroid sulfatase / Estrogen sulfotransferase / Cyp1B1 / エストロン硫酸転移酵素
Research Abstract

In the present study, we successfully prepared transgenic (TG) mice stationarily overexpressing estrogen-related enzymes consisting of aromatase (AR), steroid sulfatase (STS), estrogen sulfotransferase (EST), and 17b-hydroxysteroid dehdrogenase types I and II. We analyzed the histopathological aberration, interstitial and intracellular dynamics of estrogen metabolism, morphological and functional disorders in the organ and tissue levels, and changes of signal transduction systems and expression levels of the genes in these TG mice.
Estrogen-dependent cancers were often observed in the TG mice of AR and STS. On the other hand, cyp1B1 was reported to participate in the introduction of mutations into genomic DNA by metabolic activation of estrogens. In fact, TG mice overexpressing cyp1B1 often caused estrogen-dependent cancers. Then, we are now preparing double TG mice of AR and cyp1B1, and planning to observe susceptibility to carcinogenesis of the mice.
TG mice overexpressing EST as well … More as AR knockout mice exhibited obesity concomitant with an increased appetite probably due to decrease of intracellular levels of activated estrogens. We have previously observed abnormalities of sexual, parental, and aggressive behaviors, appearance of infanticide, decrease of locomotive (exploring) behavior, and increase of appetite in AR knockout mice. Then we introduced a human AR trangene controlled with 6.5 kb brain-specific promoter region of aromatase gene into AR knockout mice, and observed the behaviors in those mice. Although elevated levels of androgens and undetectable levels of estrogens were still observed in those mice as well as AR knockout mice, abnormal behaviors observed in the AR knockout mice were almost recovered in those mice. These results indicate that brain-specific expression (neuron-specific, hypothalamus-, preoptic area- and amygdala-specific, and perinatal period-specific expression) of aromatase and consequent brain-localized estrogens may play important roles in the organization of neuronal networks controlling these behaviors. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (21 results)

All 2005 2004

All Journal Article (21 results)

  • [Journal Article] Brain aromatase expression after experimental stroke : topography and time course.2005

    • Author(s)
      Carswell, H.V.O.
    • Journal Title

      J. Steroid Biochem. Mol. Biol. 96

      Pages: 89-91

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Analysis of spatiotemporal regulation of aromatase in the brain by transgenic mice.2005

    • Author(s)
      Harada, N.
    • Journal Title

      J. Steroid Biochem. Mol. Biol. 95

      Pages: 49-55

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activation of peroxisome proliferator-activated receptor-γ and retinoid X recepptor inhibits aromatase transcription via nuclear factor-κB.2005

    • Author(s)
      Fan, W.Q.
    • Journal Title

      Endocrinology 146

      Pages: 85-92

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Tumor-stromal interaction through the estrogen-signaling pathway in human breast cancer.2005

    • Author(s)
      Yamaguchi, Y.
    • Journal Title

      Cancer Res. 65

      Pages: 4653-4662

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Intrinsic function of the aryl hydroacarbon (dioxin) receptor as a key factor in female reproduction.2005

    • Author(s)
      Baba, T.
    • Journal Title

      Mol. Cell. Biol. 25

      Pages: 10040-10051

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lack of estrogen increases pain in the trigeminal formalin model : a behavioral and immunocytochemical study of transgenic ArKO mice.2005

    • Author(s)
      Multon, S.
    • Journal Title

      Pain 114

      Pages: 257-265

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Brain aromatase expression after experimental stroke : topography and time course.2005

    • Author(s)
      Carswell, H.V.O., etc.
    • Journal Title

      J.Steroid Biochem.Mol.Biol. 96

      Pages: 89-91

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Analysis of spatiotemporal regulation of aromatase in the brain by transgenic mice.2005

    • Author(s)
      Harada, N., etc.
    • Journal Title

      J.Steroid Biochem.Mol.Biol. 95

      Pages: 49-55

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activation of peroxisome proliferator-activated receptor-γ and retinoid X recepptor inhibits aromatase transcription via nuclear factor-κB.2005

    • Author(s)
      Fan, W.Q., etc.
    • Journal Title

      Endocrinology 146

      Pages: 85-92

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Tumor-stromal interaction through the estrogen-signaling pathway in human breast cancer.2005

    • Author(s)
      Yamaguchi, Y., etc.
    • Journal Title

      Cancer Res. 65

      Pages: 4653-4662

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction.2005

    • Author(s)
      Baba, T., etc.
    • Journal Title

      Mol.Cell.Biol. 25

      Pages: 10040-10051

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lack of estrogen increases pain in the trigeminal formalin model : a behavioral and immunocytochemical study of transgenic ArKO mice.2005

    • Author(s)
      Multon, S., etc.
    • Journal Title

      Pain 114

      Pages: 257-265

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Brain aromatase expression after experimental stroke : topography and time course.2005

    • Author(s)
      Carswell, H.V.O.
    • Journal Title

      J.Steroid Biochem.Mol.Biol. 96

      Pages: 89-91

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Analysis of spatiotemporal regulation of aromatase in the brain by transgenic mice.2005

    • Author(s)
      Harada, N.
    • Journal Title

      J.Steroid Biochem.Mol.Biol. 95

      Pages: 49-55

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Activation of peroxisome proliferator-activated receptor-y and retinoid X recepptor inhibits aromatase transcription via nuclear factor-κB.2005

    • Author(s)
      Fan, W.Q.
    • Journal Title

      Endocrinology 146

      Pages: 85-92

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction.2005

    • Author(s)
      Baba, T.
    • Journal Title

      Mol.Cell.Biol. 25

      Pages: 10040-10051

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intratumoural mRNA expression of genes from the oestradiol metabolic pathway and clinical and histopathological parameters of breast cancer2004

    • Author(s)
      Yoshimura, N.
    • Journal Title

      Breast Cancer Res. 6

      Pages: 46-55

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Relationships between aromatase activity in the brain and gonads and behavioural deficits in homozygous and heterozygous aromatase knockout mice2004

    • Author(s)
      Bakker, J.
    • Journal Title

      J.Neuroendocrinol. 16

      Pages: 483-490

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes P45017alpha and P450 aromatase localized in neurons2004

    • Author(s)
      Hojo, Y.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 101

      Pages: 865-870

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Estrogen Receptor-Independent Catechol Estrogen Binding Activity : Protein Binding Studies in Wild-Type, Estrogen Receptor-alpha KO, and Aromatase KO Mice Tissues2004

    • Author(s)
      Phillips, B.J.
    • Journal Title

      Biochemistry 43

      Pages: 6698-6708

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Restoration of male sexual behavior by adult exogenous estrogens in male aromatase knockout mice2004

    • Author(s)
      Bakker, J.
    • Journal Title

      Horm.Behav. 46

      Pages: 1-10

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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