SGER: Cloning of G Protein-Coupled Steroid Receptors

SGER：G 蛋白偶联类固醇受体的克隆

• 批准号: 9500239
• 负责人: Martin Kelly
• 金额: $ 6万
• 依托单位: Oregon Health & Science University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-15 至 1998-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9500239&HistoricalAwards=false
• 关键词: SGER; Cloning; Protein; Coupled; Steroid

Martin J. Kelly IBN-9500239 Steroid hormones play central roles in many bodily functions including neural development, reproduction, salt and water homeostasis, response to environmental stressors, skeletal maintenance and grmwth, and blood pressure to mention a few. It is generally agreed that the actions of these powerful hormones are exerted by binding to intracellular receptors which subsequently dimerize and bind to nuclear DNA where they act to facilitate or inhibit gene transcription. These actions usually take hours to days to be manifested. However, several electrophysiological and behavioral studies have reported very rapid effects of these hormones, in the seconds to minutes time frame. The rapid action of the hormones suggest that a nuclear site of action is highly unlikely and is more consistent with the existence of membrane bound G-protein-coupled receptors. Dr. Kelly has assembled a team of skilled investigators, experienced in molecular biology, behavior and electrophysiology to isolate and clone these novel steroid receptors for estrogen and glucocorticoid hormones. Using the latest in expression cloning strategies, this group proposes to isolate and characterize G-protein coupled receptors for glucocorticoids and estrogen, to study the physiological role of these novel receptors in cellular metabolism, to identify their natural ligands and begin to design agonists and antagonists for future study. This proposal is appropriate for a SGER award because these studies are novel and highly exciting. Moreover, if successful, the outcome will revolutionize our understanding of the mechanism of steroid hormones action and have major impacts in the fields of neuroscience, endocrinology and behavior.

Martin J. Kelly IBN-9500239 类固醇激素在许多身体功能中起着中心作用，包括神经发育，生殖，盐和水的稳态，对环境压力的反应，骨骼的维持和生长，以及血压等等。 人们普遍认为，这些强大的激素的作用是通过与细胞内受体结合而发挥的，细胞内受体随后二聚化并与核DNA结合，在核DNA中它们起作用以促进或抑制基因转录。 这些行动通常需要几个小时到几天才能表现出来。 然而，一些电生理和行为研究报告了这些激素的非常快速的影响，在几秒到几分钟的时间范围内。 激素的快速作用表明，作用的核位点是极不可能的，更符合膜结合G蛋白偶联受体的存在。 凯利博士组建了一个由熟练的研究人员组成的团队，他们在分子生物学，行为学和电生理学方面经验丰富，可以分离和克隆这些新的雌激素和糖皮质激素受体。 利用最新的表达克隆策略，该小组提出分离和鉴定糖皮质激素和雌激素的G蛋白偶联受体，研究这些新受体在细胞代谢中的生理作用，鉴定它们的天然配体，并开始设计激动剂和拮抗剂用于未来的研究。 这项建议是适当的SGER奖，因为这些研究是新颖的，非常令人兴奋的。 此外，如果成功，结果将彻底改变我们对类固醇激素作用机制的理解，并在神经科学，内分泌学和行为学领域产生重大影响。