STUDIES OF HORMONE ACTION IN PATIENTS WITH ALTERED G PROTEIN FUNCTION

G 蛋白功能改变患者的激素作用研究

• 批准号: 7378765
• 负责人: EMILY L GERMAIN-LEE
• 金额: $ 0.52万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378765
• 关键词: STUDIES; HORMONE; ACTION; PATIENTS; ALTERED

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The action of many hormones requires their interaction with specific cell surface receptors that are coupled by the guanine nucleotide-binding protein Gs to stimulation of adenylyl cyclase. Expression of hormones, receptors, or Gs molecules with altered biological activity can result in gain or loss of hormone actionThis protocol examines the molecular basis for altered hormone action in signal transduction pathways that utilize Gs protein as a signal transducer. These disorders include pseudohypoparathyroidism type 1a and McCune Albright syndrome due to altered expression or function of Gs, hypoparathyroidism due to defects in the calcium-sensing receptor or PTH gene, and short stature due to defects in the growth hormone-releasing hormone receptor. Biochemical and clinical characterization of the patient's phenotype facilitates a laboratory-based approach to elucidating the molecular mechanism of disease. We have evaluated the clinical and endocrine characteristics of patients with PHP type 1a to determine whether they might have deficient secretion of growth hormone (GH). We have now completed screening of 26 subjects, and have found evidence of GH deficiency in 19 subjects. These subjects are candidates for our substudy trial of hormone replacement with human recombinant GH. GH treatment has preliminarily shown an improvement in one or more of the following: height velocity, BMI, lipid profiles, and bone densities. GH deficiency may play a role in the obesity and short stature that is common in these subjects.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。许多激素的作用需要与特定的细胞表面受体相互作用，这些受体通过鸟嘌呤核苷酸结合蛋白 Gs 偶联来刺激腺苷酸环化酶。具有改变的生物活性的激素、受体或 Gs 分子的表达可以导致激素作用的获得或丧失该方案检查利用 Gs 蛋白作为信号转导器的信号转导途径中改变激素作用的分子基础。这些疾病包括由于 Gs 表达或功能改变引起的 1a 型假性甲状旁腺功能减退症和 McCune Albright 综合征、由于钙敏感受体或 PTH 基因缺陷引起的甲状旁腺功能减退症，以及由于生长激素释放激素受体缺陷引起的身材矮小。患者表型的生化和临床特征有助于采用基于实验室的方法来阐明疾病的分子机制。我们评估了 1a 型 PHP 患者的临床和内分泌特征，以确定他们是否可能存在生长激素 (GH) 分泌不足。我们现已完成对 26 名受试者的筛查，并在 19 名受试者中发现了 GH 缺乏的证据。这些受试者是我们用人类重组 GH 进行激素替代的亚研究试验的候选者。 GH 治疗初步显示出以下一项或多项方面的改善：身高增长速度、BMI、血脂和骨密度。生长激素缺乏可能与这些受试者常见的肥胖和身材矮小有关。