| Project/Area Number |
22390043
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | 東京医療学院大学 (2012)
Nippon Medical School (2010-2011) |
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Principal Investigator |
SAKUMA Yasuo 東京医療学院大学, 保健医療学部, 教授 (70094307)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Masakatsu 東京医療学院大学, 保健医療学部, 教授 (90143239)
KIYAMA Yuko 日本医科大学, 医学部, 講師 (60234390)
KONDO Yasuhiko 帝京科学大学, 生命環境学部, 准教授 (00192584)
ORIKASA Chitose 日本医科大学, 医学部, 講師 (20270671)
HAMADA Tomohiro 日本医科大学, 医学部, 助教 (90312058)
石井 寛高 日本医科大学, 医学部, 助教 (20445810)
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| Co-Investigator(Renkei-kenkyūsha) |
HAMADA Tomohiro 日本医科大学, 医学部, 助教 (90312058)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2012: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
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| Keywords | エストロゲン受容体 / 内側視索前野 / 性的二型核 / オキシトシン / 性腺刺激ホルモン放出ホルモン / GABA / ソマトスタチン / 成長加速 / プロモータ / 転写調節 / 性的二型 / 細胞移動 / GnRH / NKCC1 / 遺伝子発現制御 / 部位特異性 / 視床下部腹内側核 / 選択的細胞死 / エストロゲン / 性行動 / 性差 |
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| Research Abstract |
In rodents, activation of estrogen receptor α (ERα) determines sexual phenotype of the brain a particular stage of ontogeny. Testosterone secreted by the testes during late gestational and neonatal periods is aromatized to form estradiol in the brain. Estradiol then masculinizes the brain through genomic activation of ERα; the lack of testosterone culminates in the female phenotype. The brain sexual phenotype determines sex-specific behavior and endocrinology in adults. We have shown that the sexual differentiation of the sexually dimorphic nucleus of the preoptic area (SDN-POA), which is larger in males than in females, is accomplished by estrogen-induced neuronal migration, by using a trait of transgenic rat. In the transgenics, neurons in the SDN-POA were labeled by fluorescent protein, EGFP. Migration was visualized by time-lapse microscopy of ex vivo slice culture of the brain. Further molecular biological experiments revealed the genomic activation of ERα culminates in pho phorylation/dephosphorylation kinetics of coffilin, which eventually regulates neuronal migration by altering actin dynamics. Recordings of neuronal activity in from this structure in the non-anesthetized, free-moving rat showed association of increased neuronal activity in males engaging in sexual interaction with females. Our observation of male-typical SDN-POA in oxytocin-ligand knock-out mice, which lacks mele-typical behavior, suggested the necessity of reassessment of the function of this structure in the future.
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