Clinical/Moleular Studies of Thyroid Hormone Resistance

甲状腺激素抵抗的临床/分子研究

• 批准号: 6321814
• 负责人: FREDRIC E. WONDISFORD
• 金额: $ 10.12万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6321814
• 关键词: hormone sensitivity /resistance; human subject; molecular pathology; patient oriented research; point mutation; secretion; sign /symptom; syndrome; thyroid hormones; thyrotropin

DESCRIPTION (Taken directly from the application) The syndrome of resistance to thyroid hormone is characterized by elevated thyroid hormone levels and inappropriate TSH secretion due in almost all cases to point mutations in the TR-b locus. Studies of these naturally occurring TR mutations in vitro have yielded useful insights into the syndrome of RTH. Unfortunately, the generalizability of these studies to the patient's disorder is not always clear and because of their artificial nature may not always be secure. Confounding these issues is the clinical heterogeneity of RTH in families with the same mutation and the description of at least distinct varieties of RTH in man: generalized RTH (GRTH) and central RTH (CRTH). The goal of these studies will be to define the clinical differences between these forms of RTH and provide a molecular explanation for these differences. This proposal will allow the Principal Investigator to devote additional time to the clinical study of patients with RTH and the mentoring of new investigators entering the field of thyroid research. The candidate has recently accepted the position of Chief of Endocrinology and Professor of Medicine at the University of Chicago. He has independent support to study thyroid hormone action (R01 DK49126 and R01 DK53036) in animals and man and TRH signaling pathways in the pituitary (R01 DK50564). He directs a CRC protocol to evaluate and categorize patients with RTH. He actively mentors three BC endocrinologists in thyroid research, each having NIH K08 support for their projects. With his previous research and mentoring success, in an environment rich with academic opportunities, this award will allow him to increase his mentoring activities and to enhance his own commitment to patient-oriented research.

描述(直接从应用程序中获取) 甲状腺激素抵抗综合征的特征是甲状腺激素升高 几乎所有病例的甲状腺激素水平和不适当的TSH分泌 来指出tr-b基因的突变。这些自然发生树的研究 体外突变已经为RTH综合征提供了有用的见解。不幸的是，这些研究对患者障碍的概括性 并不总是清晰的，因为它们的人工本性可能并不总是 安全。混淆这些问题的是RTH在临床上的异质性 具有相同突变和至少不同描述的家系 人类RTH的种类：广泛性RTH(GRTH)和中枢性RTH(CRTH)。这个 这些研究的目标将是确定这两种疾病之间的临床差异 并为这些差异提供了分子解释。这 建议将使首席调查员有更多时间 RTH患者的临床研究及新研究者的指导 进入甲状腺研究领域。这位候选人最近接受了 大学内分泌学主任和医学教授的职位 来自芝加哥。他有独立的支持来研究甲状腺激素的作用(R01 DK49126和R01 DK53036)和人类的TRH信号通路 脑垂体(R01 DK50564)。他指导了一项CRC协议来评估和分类 RTH患者。他积极指导不列颠哥伦比亚省的三位甲状腺内分泌学家 研究，每个都有NIH K08对他们的项目的支持。与他的前妻 在一个充满学术知识的环境中，研究和指导取得成功 机会，这个奖项将允许他增加他的指导活动 并加强自己对以患者为中心的研究的承诺。