CAREER:Relevance of non-genomic estrogen signaling to neuromorphology and aggressive behavior

职业：非基因组雌激素信号传导与神经形态和攻击行为的相关性

• 批准号: 1053716
• 负责人: Nandini Vasudevan
• 金额: $ 100万
• 依托单位: Tulane University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1053716&HistoricalAwards=false
• 关键词: CAREER; Relevance; non; genomic; estrogen

Estrogen, a steroid hormone is important for reproduction, social behaviors, cognition and the progression of several diseases such as breast and ovarian cancers. It influences these processes by binding a specific receptor, the estrogen receptor (ER) alpha or the ER beta. Traditionally, these receptors reside within cells and signal by slowly regulating the transcription of target genes. However, estrogen can also rapidly activate kinases and increase calcium within cells via putative receptors on the cell membrane. Dr. Vasudevan has previously demonstrated that estrogen, acting rapidly at the cell membrane can couple to increased transcription in the nucleus. This suggests that a novel integrated signaling pathway linking rapid cell membrane-initiated signaling to nuclear transcription is driven by estrogen in neurons. This project will elucidate various components of this signaling pathway; starting with the idea that coupling occurs via ER alpha phosphorylation. The importance of modification of the ER alpha that directly impacts ER alphafunction will be examined. Lastly, the importance of this pathway in known estrogen-mediated changes in aggressive behavior and neuromorphology will also be examined. Molecular biological approaches using ER in cell culture, and histochemical and behavioral analysis in animal models will be used to understand the significance of coupled-signaling. Understanding this pathway in the framework of biological function will close a critical gap in our understanding of this controversial mode of estrogen signaling and introduce a new paradigm in steroid receptor biology, applicable to any hormone responsive tissue. The activities in this project provide research opportunities not only for graduate students, but also for K-12 students and undergraduates, particularly those from minority and under-represented groups. In addition, undergraduates and graduates will gain exposure and global experience in international collaborations, scientific meetings and by authoring research publications.

雌激素是一种类固醇激素，对生殖、社会行为、认知以及乳腺癌和卵巢癌等多种疾病的进展都很重要。 它通过结合特定的受体，雌激素受体（ER）α或ER β来影响这些过程。 传统上，这些受体存在于细胞内，并通过缓慢调节靶基因的转录来发出信号。 然而，雌激素也可以通过细胞膜上的假定受体快速激活激酶并增加细胞内的钙。 Vasudevan博士先前已经证明，雌激素在细胞膜上迅速起作用，可以与细胞核中的转录增加相结合。这表明，一个新的整合信号通路连接快速细胞膜启动的信号核转录是由雌激素在神经元。 这个项目将阐明这个信号通路的各种组成部分;从通过ER α磷酸化发生偶联的想法开始。 将检查直接影响ER α功能的ER α修饰的重要性。 最后，这一途径在已知的雌激素介导的攻击行为和神经形态学的变化的重要性也将进行检查。 在细胞培养中使用ER的分子生物学方法，以及在动物模型中的组织化学和行为分析将用于理解偶联信号的意义。 在生物学功能的框架中理解这一途径将缩小我们对这种有争议的雌激素信号传导模式的理解中的一个关键差距，并在类固醇受体生物学中引入一种新的范式，适用于任何激素反应组织。 该项目的活动不仅为研究生，而且为K-12学生和本科生，特别是来自少数民族和代表性不足群体的学生提供了研究机会。 此外，本科生和毕业生将获得国际合作，科学会议和创作研究出版物的曝光和全球经验。