孤儿核受体:将内分泌学转向逆向
S A Kliewer1, J M Lehmann, T M Willson
1Department of Molecular Endocrinology, Glaxo Wellcome Research and Development, Five Moore Drive, Research Triangle Park, NC 27709, USA. sak15922@glaxowellcome.com
概括
核受体,包括孤儿受体,是通过类固醇和视网类激素等激素对基因调节的关键. 识别新的连接体揭示了具有显著生理影响的新信号通路.
科学领域:
- 内分泌学和分子生物学
- 基因调控和转录因子
背景情况:
- 类固醇,甲状腺激素和视网 (维生素A代谢物) 通过核受体控制基因表达.
- 核受体是联体激活的转录因子,包括没有已知的联体的"孤儿"成员.
- 孤儿核受体是发现新信号通路的潜在目标.
研究的目的:
- 探索孤儿核受体在生物系统中的作用.
- 研究"逆内分泌学"方法的实用性,以确定新的核受体连接体和途径.
- 了解新发现的核信号通路的生理和药理意义.
主要方法:
- 使用"逆内分泌学"策略来识别孤儿核受体的天然和合成配体.
- 使用这些已识别的配体来剖析各自受体的生物功能.
- 研究这些核信号通路对生理过程的影响.
主要成果:
- 成功识别了几个孤儿核受体的配体.
- 这些联结受体介导的生物作用的剖析.
- 发现了以前未知的核信号通路,其中包括视网,脂肪酸,eicosanoids和类固醇.
结论:
- "逆内分泌学"的方法对于发现新的核受体配体和功能是有效的.
- 由核受体调节的新信号通路具有显著的生理和药理影响.
- 这种策略扩大了我们对内分泌信号的理解,并提供了治疗潜力.
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