| Project/Area Number |
17K08402
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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 and hygienic pharmacy
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| Research Institution | Hiroshima International University |
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Principal Investigator |
Takeda Shuso 広島国際大学, 薬学部, 准教授 (00460379)
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| Project Period (FY) |
2017-04-01 – 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 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | エストロゲン受容体 / スプライスバリアント / 抗エストロゲン作用 / 毒性指標 / ビスフェノールAF / エストロゲン受容体β / 環境化学物質 |
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| Outline of Final Research Achievements |
Estrogens including estradiol utilize estrogen receptors (ERs) α/β to evoke a number of physiological effects as ligands. Many endocrine-disrupting chemicals (EDCs) have been known to exhibit estrogenic/anti-estrogenic activities, which are, at least in part, mediated by the two ERs. EDCs have been shown to modulate estrogen signaling in two manners: i) a direct/indirect interaction with ERs and ii) the up-/down-regulation of ERs.
Bisphenol AF (BPAF) is recognized as one of the replacements for bisphenol A (BPA). Although considerable experimental evidence suggests that BPA is an EDC, the toxicological profile of BPAF has not fully investigated. In this study, we demonstrated that i) BPAF functioned as a stimulator of ERβ1 (in addition to ERα), ii) the stimulation of ERβ1 by BPAF was abrogated by PHTPP (an ERβ selective antagonist), and iii) the expression of ERβ1 and ERβ2 was not modulated by BPAF at nanomolar concentrations.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は衛生薬学を志向している。これは「健康体を病気にしないサイエンス」である。氾濫する化学物質の中でも、慢性的に長期間曝露されることで、悪影響がはじめて現れる例があり、代表例として内分泌かく乱物質がある。本研究では、独自に見出だした知見を応用し、環境化学物質による女性ホルモン作用かく乱の分子機構をERβ(エストロゲン受容体)の発現変動に注目して解明することを目指した。得られた知見は、毒性学の観点からもリスク評価系の構築に貢献することが考えられる。
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