Molecular basis of low-dose effects based on super enhancer transcriptional regulation on nuclear receptors induced by in utero exposure of next-generation bisphenol derivatives

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H00635
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 63:Environmental analyses and evaluation and related fields
• Research Institution: Kyushu University
• Principal Investigator: Matsushima Ayami 九州大学, 理学研究院, 准教授 (60404050)
• Co-Investigator(Kenkyū-buntansha): 瀬々 潤 株式会社ヒューマノーム研究所, 本社, 代表取締役社長 (40361539)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 発現制蛋白質 / 生体分子 / 受容体化学 / 人体有害物質 / 内分泌かく乱物質 / 生物活性分子 / 微量化学物質 / 活性発現の分子機構

Outline of Final Research Achievements

Bisphenol A, which is used worldwide as an industrial raw material for plastics, is also a toxic environmental chemical with adverse effects from exposure at very low doses. Their targets are estimated to be nuclear receptors that exist in the cell nucleus and regulate gene transcription. Therefore, bisphenol A derivatives are increasingly being used as substitutes for bisphenol A. In this study, we found that bisphenol A derivatives bind to the estrogen receptors more strongly than bisphenol A. Furthermore, we elucidated that it acts as a coactivator binding inhibitor for the estrogen receptor β. This is the first report of an environmental chemical acting as a coactivator-binding inhibitor.

Free Research Field

生物化学、受容体科学、リスクサイエンス

Academic Significance and Societal Importance of the Research Achievements

文明社会においては、多種多様な化学物質が環境中に放出されている。これらの環境化学物質の安全性評価は、ヒトの健康と環境のために重要である。現在、有害環境化学物質ビスフェノールAが示す、生殖系のみならず脳神経でも発現する悪影響の分子メカニズムは未解明である。本研究では、この解明の端緒として、ビスフェノールA誘導体が、転写共役因子阻害剤として働くことを明らかにするなど、有意義な研究成果を得た。