Generation of estrogen membrane receptor-deficient rat by genome editing and elucidation for the mechanism of anti-mitogenic action
| Project/Area Number |
16K08522
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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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 | Tokoha University (2019)
University of Yamanashi (2016-2018) |
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Principal Investigator |
Mitsui Tetsuo 常葉大学, 社会環境学部, 准教授 (20402084)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | Estrogen / Gpr30 / Lactotroph / Proliferation / エストロジェン / 膜受容体 / 細胞増殖 / 下垂体 / 遺伝子発現 / ゲノム編集 / 遺伝子 / シグナル伝達 |
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| Outline of Final Research Achievements |
Estrogen binds to nuclear estrogen receptors (ERs) to modulate transcription of target genes in estrogen-responsive cells. However, recent studies have shown that estrogen also binds to cytoplasmic membrane ERs to modulate protein kinase signaling cascades, leading to non-genomic actions. We investigated whether either nuclear or membrane ERs, including G protein-coupled receptor 30 (Gpr30), mediate the inhibitory action of estrogen on insulin-like growth factor-1 (IGF-1)-induced proliferation of pituitary lactotrophs in primary culture. Activation of Gpr30 by its agonist G-1 inhibited IGF-1-induced proliferation in a dose-dependent manner, but it had little effect on modulation of mRNA expression of estrogen-responsive genes. Here, we demonstrate that E2 inhibition of lactotroph proliferation is due to nuclear ER-mediated genomic action. Our results suggest that activation of Gpr30 mimics, but does not mediate, the anti-proliferative action of E2 on lactotrophs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、多くのエストロジェン感受性細胞において、従来増殖促進作用によってのみ説明されていた増殖調節機構の理解に新しい展開をもたらす可能性がある。
エストロジェン感受性腫瘍の従来の治療ストラテジーはエストロジェンの増殖促進作用を阻害することに限定されていたが、エストロジェンの膜受容体Gpr30を介した増殖調節機構の解明は、エストロジェンの増殖抑制作用を増強することを目指す、まったく新しい治療ストラテジーを提唱することができる。この点において、エストロジェン感受性腫瘍に関する臨床的意義も大きいと考えられる。
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Report
(5 results)
Research Products
(9 results)
