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Mechanism of brain sexual differentiation by regulation of aromatase and sex-steroid receptors.

Research Project

Project/Area Number 08458262
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionYamaguchi University (1998)
Kinki University (1996-1997)

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) NAKAHAMA Ken-ichi  Kinki University School of Medicine, Instructor, 医学部, 助手 (60281515)
NAGANO Mamoru  Kinki University School of Medicine, Instructor, 医学部, 助手 (80155960)
OTSUKI Tsukasa  Yamaguchi University School of Medicine, Instructor, 医学部, 助手 (70243631)
KAWATA Keisuke  Yamaguchi University School of Medicine, Instructor, 医学部, 助手 (20284242)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1998: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥6,900,000 (Direct Cost: ¥6,900,000)
Keywordsestrogen / androgen / sexual behavior / sexual differentiation / estrogen receptor / androgen receptor / medial preoptic area / medial amygdala / 内側視索前野扁桃体弓 / アロマテ-ス / 性ホルモン / 扁桃体 / ステロイドレセプター / 内側視策前野
Research Abstract

The presence of neuronal aromatase has been immunohistochemically determined in the aldehyde-fixed rat and monkey brains. The most striking aromatase-immunoreactive (AROM-I) neurons are present in the medial preoptico-amygdaloid neuronal arcs (mPOAM arcs) in both animals. The regions have been considered as centers of reproductive functions and larger in size in males than in females, confirming that intracranial estrogen-biosynthesis is essential to development of reproductive neural substrates and functions in mammals. They appear by E15 in the rat, reaching a peak in staining intensity between El 8-P2 and diminishing after the perinatal stage. Expression in the mPOAM arc are clearly more prominent in males in number and immunoreactivity than in females, especially after young-to-adult stages. The AROM-I neurons have also been clarified to show sexually dimorphic expression for both alpha-estrogen and androgen receptors (EsR and AnR). In neonates, expression of EsR in the mPOAM arc i … More s already more prominent in females than in males, whereas that of AnR is more prominent in males than in female. In young-to-adult stages, the sexually dimorphic expressions are further enhanced in accordance with increased expressions of EsR in females or AnR in males during adolescence. Neonatal castration in male rats was found to change the male's pattern to the female's one with respect to AROM, EsR and AnR in the mPOAM arc. Administration of 5alpha-dihydrotestosterone strongly increases the expressions of AROM and AnR and slightly increase EsR, while 17beta-estradiol slightly increases the expressions of AROM and AnR and strongly decreases the expression of EsR.Testosterone strongly increases the expressions of AROM and AnR, and strongly decreases the expression of EsR in the mPOAM arc, indicating that only testosterone can recovered expression of the male pattern in the neonatally castrated male rats. Thus, some testosterones are considered to be actually aromatized into estradiol and to down-regulate EsR, while others sparing aromatization can act directly on AnR in the mPOAM arc. A complete male probably requires not only masculinization by enhancement of an AnR-stimulation via the up-regulation of AnR but also defeminization by reduction of an EsR-stimulation via the down-regulation of EsR in the Iimbic arc. Less

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Shinoda, K.: "A critical role of neuronal aromatase in brain sexual differentiation." Brain Medical. 8. 273-279 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sasaki, H: "Effects of extracelluler matrix macromolecules on the differentiation of plasma membrane" Cell Structure and Function. 21. 133-141 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 篠田 晃: "脳内エストロゲン合成ニューロンと脳の性分化" 山口医学. 47. 163-164 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakahama, K: "Effect of TPA on aquaporin 4 mRNA expression in cultured rat astrocytes." Glia. 25. 240-246 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shinoda, K: "A new concept for brain aromatase in sexual differentiation" Proceeding of 14th TMIN international symposium. 14. 36-39 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shinoda, K.: "A critical role of neural aromatase in brain sexual differentiation." Brain Med.8. 273-279 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sasaki, H et al.: "Effects of extracellular matrix macromolecules on the differentiation of plasma membrane structure in cultured astrocytes." Cell Structure and Function. 21. 133-141 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shinoda, K.: "Intracranial estrogen-synthesis and brain sexual differentiation." Yamaguchi Medical Journal. 47. 163-164 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shinoda, K.: "A new concept for brain aromatase in sexual differentiation. ; novel answers to classic questions : development and differentiation of neuroendocrine system." Proceeding of 14th TMIN International Symposium. 36-39 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakahama, K.et al.: "Effect of TPA on apuaporin 4 mRNA expression in cultured rat astrocytes." Glia. 25. 240-246 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 篠田晃: "脳内エストロゲン合成と脳の性分化" 山口医学. 47. 163-164 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shinoda,K: "A new concept for brain aromatase in sexual differentiation" Proceeding of 14th TMIN international symposium. 14. 36-39 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakahama,K: "Effect of TPA on aquaporin 4 mRNA expression in cultured rat astrceytes" Glia. 25. 240-246 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 篠田晃: "脳の性分化における芳香化酵素の役割" Brain Medical特集「脳の男女差」. 8巻3号. 273-279 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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