Untersuchung des Zusammenspiels zwischen Estrogenrezeptoren und AhR nuclear translocator (ARNT).

研究雌激素受体与 AhR 核转位子 (ARNT) 之间的相互作用。

• 批准号: 13656523
• 负责人: Dr. Joelle Rüegg
• 金额: --
• 依托单位: Institutionen för biovetenskap och näring
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/13656523?language=en
• 关键词: Untersuchung; des; Zusammenspiels; zwischen; Estrogenrezeptoren

Estrogens are steroid hormones and regulate many vital physiological processes. Their effects are mediated by two estrogen receptors (ER), ER¿ and ERß which regulate expression of target genes following binding of the ligand. Contaminants in the environment can interfere with the function of ERs and thereby cause deleterious effects in the body. One such contaminant is dioxin which is an environmental pollutant formed through incomplete combustion of waste. The biological effects of dioxin are mediated by the Aryl hydrocarbon receptor (AhR) that belongs to the family of basic helix-loop-helix (bHLH)-PAS transcriptional regulators. To become active, AhR must not only bind to dioxin but additionally to its partner AhR nuclear translocator (ARNT), another bHLH-PAS protein. Recently, it has been shown that ARNT can also act as co-activator of ER, i.e. increased amounts of ARNT enhance ER activity. This finding suggests that the interference of dioxin with the ER function is at least partly due to a competition between ER and AhR for the common co-activator ARNT. The aim of this project is to investigate this hypothesis by elucidating the interplay between ARNT and ER. This should be achieved by firstly testing whether ARNT up- and down-regulation affects the effects of dioxin on ER function, and secondly investigating the involvement of additional factors in the ARNT-ER interplay, namely other co-activators of ER. This should lead to a better understanding of the harmful effects of dioxin and might broaden our knowledge about the action of environmental contaminants in general.

雌激素是类固醇激素，调节许多重要的生理过程。它们的作用由两种雌激素受体（ER）介导，ER β和ER β在配体结合后调节靶基因的表达。环境中的污染物会干扰ER的功能，从而对人体造成有害影响。其中一种污染物是二恶英，这是一种通过废物不完全燃烧形成的环境污染物。二恶英的生物学效应是由属于碱性螺旋-环-螺旋（bHLH）-PAS转录调节因子家族的芳烃受体（AhR）介导的。为了变得有活性，AhR不仅必须与二恶英结合，还必须与另一种bHLH-PAS蛋白质AhR核转运蛋白（ARNT）结合。最近，已经表明ARNT也可以作为ER的共激活剂，即增加量的ARNT增强ER活性。这一发现表明，二恶英与ER功能的干扰至少部分是由于ER和AhR之间的竞争，共同的辅激活剂ARNT。本项目的目的是通过阐明ARNT和ER之间的相互作用来研究这一假说。这应该通过以下方式实现：首先测试ARNT上调和下调是否影响二恶英对ER功能的影响，其次调查ARNT-ER相互作用中其他因素的参与，即ER的其他共激活剂。这将使我们更好地了解二恶英的有害影响，并可能扩大我们对环境污染物一般作用的了解。