REGULATION OF THYROID FUNCTION T4 AND T3 KINETICS

甲状腺功能 T4 和 T3 动力学的调节

• 批准号: 3226225
• 负责人: Lewis Braverman
• 金额: $ 29.68万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-12-01 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3226225
• 关键词: amiodarone; autoimmune disorder; disease /disorder model; embryo /fetus; endocrine disorder chemotherapy; female; hormone metabolism; hormone receptor; hormone regulation /control mechanism; human subject; hyperthyroidism; hypothyroidism; immunosuppressive; insulin dependent diabetes mellitus; interferons; iodination; iodine; laboratory rat; lymphomatous thyroiditis; neuropeptides; newborn animals; nutrition related tag; placental transfer; radioimmunoassay; radionuclides; radiotracer; thalidomide; thyroid function; thyroid hormone binding protein; thyroid inhibitor; thyrotropin; thyroxine; triiodothyronine

Past and proposed work in this laboratory have included the following major areas of clinical and basic research: metabolism, protein binding and peripheral effects of the thyroid hormones (TH); regulation of TSH secretion; effects of iodine on thyroid function in man and rodents; and immunological aspects of thyroid pathophysiology. A synthetic flavonoid, EMD 21388 (F), which inhibits the serum protein binding (TBPA) of the TH and 5'- deiodinase activity (5'-D) in vitro will be utilized to study, in the rat, the in vivo effects of rapid displacement of the TH from their major serum binding protein (TBPA) in peripheral tissues, the possible thyromimetic effects of F in vivo and in vitro (using GH producing tumor cell lines), and the possible in vivo and in vitro inhibitory effects of F on 5'-D. Starvation and other experimental conditions in the rat are associated with the appearance of serum TBG (rTBG), and preliminary studies suggest an enhanced response in females compared to males. This will be further investigated to determine the possible etiology of this finding. The prevalence of Familial Dysalbuminemic Hyperthyroximenia (FDH), which appears to be relatively common, especially in Puerto Rican families, will be determined by studying families of newborns whose serum T4 concentration is at least 2SD above the mean. The role of iodine intake on the prevalence of thyroid dysfunction in the elderly and in the pathogenesis of autoimmune thyroid diseases in man and in the diabetes prone BB/Wor rat will continue to be addressed. New immunosuppressant drugs (thalidomide and ciamexone) will be used in an attempt to prevent the occurrence of spontaneous and iodine induced lymphocytic thyroiditis (LT) in the BB/Wor rat. This model will also be used to determine whether, as in humans, transient LT is common during the post partum period. Finally, preliminary retrospective studies suggest that chronic levothyroxine therapy for hypothyroidism and for TSH suppression in premenopausal women enhances bone loss. A prospective study is now planned to confirm these observations. The overall aims of this proposal is to provide further information on the binding and peripheral metabolism and effects of the TH and to further delineate the role of iodine and class II (Ia) antigen in the etiology of autoimmune thyroid disease in man and rat.

该实验室过去和拟议的工作包括 主要临床和基础研究领域如下： 甲状腺的代谢、蛋白质结合和外周效应 激素（TH）；调节 TSH 分泌；碘对的影响 人类和啮齿动物的甲状腺功能；和免疫学方面 甲状腺病理生理学。 一种合成类黄酮，EMD 21388 (F)， 抑制 TH 和 5'- 的血清蛋白结合 (TBPA) 体外脱碘酶活性 (5'-D) 将用于研究 在大鼠中，TH 快速移位的体内效应 外周组织中的主要血清结合蛋白（TBPA）， F在体内和体外可能的拟甲状腺作用 （使用产生 GH 的肿瘤细胞系），以及可能的体内 以及F对5'-D的体外抑制作用。 饥饿和 大鼠的其他实验条件与 血清 TBG (rTBG) 的出现，初步研究表明 与男性相比，女性的反应增强。 这将是 进一步研究以确定这种情况的可能病因 发现。 家族性白蛋白血症的患病率 高甲状腺素血症（FDH）似乎相对常见， 特别是在波多黎各家庭中，将由 研究血清 T4 浓度为 至少比平均值高 2SD。 碘摄入量对身体的作用 老年人和老年人甲状腺功能障碍的患病率 人类自身免疫性甲状腺疾病的发病机制 易患糖尿病的 BB/Wor 大鼠将继续得到解决。 新的 将使用免疫抑制剂（沙利度胺和希美松） 以防止自燃和碘的发生 在 BB/Wor 大鼠中诱导淋巴细胞性甲状腺炎 (LT)。 这 模型还将用于确定是否像人类一样， 短暂性 LT 在产后期间很常见。 最后， 初步回顾性研究表明，慢性 左旋甲状腺素治疗甲状腺功能减退症和 TSH 抑制 绝经前妇女会增加骨质流失。 一项前瞻性研究 现在计划确认这些观察结果。 总体目标 该提案的目的是提供有关具有约束力的进一步信息 以及 TH 的外周代谢和影响，并进一步 描述碘和 II 类 (Ia) 抗原在 人和大鼠自身免疫性甲状腺疾病的病因学。