STEROIDS REPRESS LH THROUGH PROTEIN/PROTEIN INTERACTIONS

我的近期目标是发展一个平等的研究背景， 我已经致力于临床工作。 因此，我决定追求 博士学位与约翰尼尔森博士在凯斯西储 大学（CWRU）。 我的长期职业目标是将我的才能联合收割机 在基础科学和临床医学方面担任教职， 兽医教学机构。 尼尔森博士实验室的项目 和环境在CWRU提供非凡的访问任何所需的 资源 我的研究生涯发展将在此得到培育 环境，可参加许多结构化会议和培训 机会 在这里，我将学习如何批判性地评估数据， 能让我设计出符合逻辑的新实验 此外，我将 在写作简洁和有意义方面接受了宝贵的训练 科学研究论文和拨款申请。这些成绩 我的最终目标是成为一个独立的人， 研究员 这项拨款解决了总体工作假设，即雄激素 雌激素受体通过多种途径抑制促黄体生成素的表达 促性腺激素的蛋白质相互作用。证据表明 促性腺激素中的AR通过以下途径抑制α亚基启动子 蛋白质-蛋白质相互作用涉及两种不同的调节 元素 然而，这些关键蛋白质的身份仍然是 未知 在目标1中，酵母双杂交方法将用于两者 一种定向和随机的方式来筛选辅阻遏蛋白。 在 此外，我们假设，至少有一个磷酸化的残基， AR是与辅阻遏蛋白成功相互作用所必需的。 我们打算在目标2中测试这一假设， AR磷酸化突变体与α亚单位启动子在 促性腺细胞 最后，我们计划利用从 α亚单位抑制机制，使我们能够解锁 LH β调节背后的奥秘 在目标3中，我们建议设计 转基因小鼠，以确定网站和机制， LH β亚基基因的类固醇生成调控。

My immediate goal is to develop an equal background in research to what I had already devoted to clinical work. Therefore, I decided to pursue a doctoral degree with Dr. John Nilson at Case Western Reserve University (CWRU). My long term career goals are to combine my talents in basic science and clinical medicine in a faculty position at a veterinary teaching institution. The program in Dr. Nilson's laboratory and the environment at CWRU provide extraordinary access to any required resources. My research career development will be nurtured in this environment with the access to numerous structured meetings and training opportunities. Here I will learn how to critically evaluate data which will allow me to plan logical new experiments. In addition, I will receive invaluable training in writing succinct and meaningful scientific research papers and grant proposals. These achievements are critical in striving for my ultimate goal of becoming an independent researcher. This grant addresses the overall working hypothesis that the androgen and estrogen receptors repress lutropin expression through multiple protein-protein interactions in gonadotropes. Evidence indicates that AR in gonadotropes suppresses the alpha subunit promoter through protein-protein interactions that involve two distinct regulatory elements. However the identity of these critical proteins remains unknown. In Aim 1, the yeast two-hybrid approach will be used in both a directed and random fashion to screen for co-repressor proteins. In addition, we postulate that at least one phosphorylated residue of the AR is required for successful interaction with the co-repressor protein. We intend to test this hypothesis in Aim 2 by transiently transfecting AR phosphorylation mutants with the alpha subunit promoter in gonadotrope cells. Finally, we plan to exploit the knowledge gained on the alpha subunit suppression mechanism to enable us to unlock the mystery behind LHbeta regulation. In Aim 3, we propose to design transgenic mice in order to define the site and mechanism of steroidogenic regulation on the LHbeta subunit gene.