RESISTANCE TO THYROID HORMONE

对甲状腺激素的抵抗

• 批准号: 7604743
• 负责人: ROY E WEISS
• 金额: $ 1.35万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604743
• 关键词: Biological; Cell Nucleus; Cell membrane; Clinical Protocols; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Condition; Defect; Diagnosis; Early Intervention; Funding; Gene Mutation; Genetic screening method; Glucocorticoids; Grant; Institution; Mediating; Mutation; Neurologic; Nuclear; Nuclear Receptors; Organ; Phenotype; Prenatal Diagnosis; Receptor Gene; Research; Research Personnel; Resistance; Resources; Source; Syndrome; Testing; Thyroid Function Tests; Thyroid Hormones; Thyroxine; Transmembrane Transport; Triiodothyronine; United States National Institutes of Health; base; cofactor; prevent; prohormone; receptor

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 objectives of this clinical investigation are to establish and test clinical protocols that will serve to evaluate syndromes of resistance to thyroid hormone as defined in the broadest sense. Resistance to thyroid hormone are syndromes of reduced end-organ responsiveness to thyroid hormone. Conditions under consideration encompass those physioloigcal defects that interfere with the biological activity of a chemically intact thyroid hormone supplied in normal amount. These include: 1) Abnormalities in cell membrane transport of thyroid hormone; 2) Abnormalities in the conversion of the prohormone 3,3 ,5,5 -tetraiodothyronine (thyroxine, T4) into the active thyroid hormone, 3,3 ,5-triiodothyronine (T3) and 3) Abnormalities at the level of nuclear action of T3 due to TH receptor (TR)? defects, known as the classical resistance to thyroid hormone (RTH) or similar syndromes without TR? gene mutations. The latter, termed nonTR-RTH, are associated with abnormalities in cofactors mediating the action of thyroid hormone at the nucleus. These cofactors are common to related nuclear receptors, and it is postulated that they may also produce subtle resistance to glucocorticoid action. These defects may be suspected based on thyroid function tests. However basal thyroid function tests are not sufficient to make an accurate diagnosis and require a careful analysis of the subject s phenotype as proposed in this application. Furthermore characterization of the phenotypes of these syndromes would establish criteria for genetic testing which in turn could allow for prenatal diagnosis and possibly early intervention and treatment. This would be particularly important in defects that are associated with significant neurologic sequelae (e.g. MCT8 mutations) where early intervention may reverse or prevent the associated findings.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本临床研究的目的是建立和测试临床方案，用于评价最广义定义的甲状腺激素抵抗综合征。 甲状腺激素抵抗是终末器官对甲状腺激素反应性降低的综合征。 所考虑的条件包括那些生理缺陷，干扰正常量的化学完整的甲状腺激素的生物活性。 其中包括：1）甲状腺激素的细胞膜转运功能障碍，2）甲状腺素原（T_4）向活性甲状腺激素（T_3）转化功能障碍，3）T_3通过TH受体（TR）的核作用水平障碍。缺陷，被称为经典的甲状腺激素抵抗（RTH）或类似的综合征没有TR？基因突变 后者称为nonTR-RTH，与介导甲状腺激素在细胞核作用的辅因子异常有关。这些辅因子是相关核受体所共有的，据推测它们也可能对糖皮质激素的作用产生微妙的抵抗。 这些缺陷可能是根据甲状腺功能测试怀疑。 然而，基础甲状腺功能测试不足以做出准确的诊断，并且需要仔细分析受试者的表型，如本申请中所提出的。 此外，这些综合征的表型特征将建立基因检测的标准，这反过来又可以允许产前诊断和可能的早期干预和治疗。 这对于与显著神经系统后遗症（例如MCT 8突变）相关的缺陷尤其重要，早期干预可能会逆转或预防相关发现。