TSH RECEPTOR AUTOREGULATION

TSH 受体自动调节

• 批准号: 9887511
• 负责人: TERRY Francis DAVIES
• 金额: --
• 依托单位: JAMES J PETERS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9887511
• 关键词: Active Sites; Adipocytes; Agonist; Antibodies; Antigens; Autoimmune Process; Binding; Biology; Bioluminescence; Body part; CRISPR/Cas technology; Cell physiology; Cells; Characteristics; Co-Immunoprecipitations; Cytometry; Development; Disease; Energy Transfer; Eye; Fatty acid glycerol esters; Fibroblasts; Fluorescence; Fluorescence Resonance Energy Transfer; Funding; GTP-Binding Proteins; Graves' Disease; Growth and Development function; Homeostasis; Human; Hyperthyroidism; Immune; Immune response; Immunoblotting; Immunohistochemistry; Immunologic Receptors; Insulin-Like Growth Factor Receptor; Knockout Mice; Knowledge; Learning; Life Cycle Stages; Ligands; Link; Mainstreaming; Malignant neoplasm of thyroid; Mass Spectrum Analysis; Membrane Microdomains; Messenger RNA; Molecular; Monitor; Muscle; Operative Surgical Procedures; Osteoblasts; Osteoclasts; Pathway interactions; Patients; Phenotype; Phosphorylation; Physiology; Population; Preparation; RNA Splicing; Receptor Gene; Receptor Signaling; Role; Route; Signal Transduction; Site; Skin; Small Interfering RNA; Suspensions; System; TSH receptor antibody; Testing; Thyroid Diseases; Thyroid Gland; Thyroid Hormones; Thyrotropin Receptor; Tissues; Transactivation; Variant; Veterans; Woman; autoimmune thyroid disease; bone; bone cell; design; dimer; experience; glycosylation; immunoreactivity; inhibitor/antagonist; men; novel; protein activation; receptor; receptor expression; small molecule; src-Family Kinases; thyroid associated ophthalmopathies; trafficking; tumor

SUMMARY The thyroidal TSH receptor (TSHR) is the major control point for thyroid hormone synthesis and release as well as thyroid growth and development and is also expressed in a wide variety of non- thyroid tissues including adipocytes, fibroblasts, osteoclasts, osteoblasts and immune cells. The TSHR is a major antigen in autoimmune thyroid disease, especially Graves' disease. However, the mechanisms by which the TSHR modulates non-thyroidal cells is largely unclear and the autoimmune role of extra-thyroidal TSHRs mostly unknown. In this submission, we intend to explore the detailed biology and immune role of selected extra-thyroidal TSHRs aided by our extensive experience with TSHR analysis in thyroid cells. We have 3 specific aims: Specific Aim 1- Explore the molecular characterization, posttranslational processing and receptor routing of TSHRs in extra-thyroidal human cells. Specific Aim 2- Examine the promiscuity of heterologous receptor interactions and study TSHR transactivation. Specific Aim 3- Analyze the immunoreactivity of extra thyroidal TSHRs Although the thyroidal TSHR has been extensively explored, the recognition of extra-thyroidal TSHR expression has revealed a large gap in our knowledge. Information already generated suggests that such sites are active and modulate receptor biology and disease as our studies on bone cells and TSHR-KO mice have illustrated. However, concerns that such TSHRs are immunologically suppressed remain unexplored. Large gaps in our knowledge of the receptor biology of these extra thyroidal tissues exist and our studies will begin to clarify some of these questions.

概括 甲状腺TSH受体（TSHR）是甲状腺激素合成和 释放以及甲状腺的生长和发育，也以多种非 - 甲状腺组织，包括脂肪细胞，成纤维细胞，破骨细胞，成骨细胞和免疫细胞。这 TSHR是自身免疫性甲状腺疾病的主要抗原，尤其是Graves疾病。然而， TSHR调节非甲状腺细胞的机制在很大程度上不清楚，并且 甲状腺外TSHR的自身免疫作用主要未知。在此提交中，我们打算 探索由我们的详细生物学和免疫作用 甲状腺细胞中TSHR分析的丰富经验。我们有3个具体目标： 特定目的1-探索分子表征，翻译后处理 TSHRS在甲状腺外人类细胞中的受体路由。 特定目标2-检查异源受体相互作用和 研究TSHR反式激活。 特定目标3-分析甲状腺额外TSHR的免疫反应性 尽管甲状腺TSHR已被广泛探索，但甲状腺外的识别 TSHR表达在我们的知识上揭示了很大的差距。信息已经生成 表明此类部位是主动的，并且调节受体生物学和疾病，作为我们的研究 骨细胞和TSHR-KO小鼠已经说明了。但是，担心这样的TSHR是 在免疫学上抑制仍然没有探索。我们对受体的了解的巨大差距 这些额外的甲状腺组织的生物学存在，我们的研究将开始阐明其中一些 问题。