REGULATION OF THYROID FUNCTION T4 AND T3 KINETICS

本实验室过去和拟议的工作包括 以下是临床和基础研究的主要领域： 甲状腺的代谢、蛋白结合和外周效应 甲状腺激素;促甲状腺激素分泌调节;碘对甲状腺功能的影响 人类和啮齿类动物的甲状腺功能; 甲状腺病理生理学 一种合成类黄酮，EMD 21388（F）， 其抑制TH和5 '-HT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从 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GH产生肿瘤细胞系），以及可能的体内 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 女性的反应比男性强 这将是 进一步研究以确定可能的病因 发现 家族性白蛋白血症的患病率 甲状腺机能亢进症（FDH），这似乎是相对常见的， 特别是在波多黎各家庭，将由 研究血清T4浓度在 高于平均值至少2SD。 碘摄入量对 老年人和老年人甲状腺功能障碍的患病率 自身免疫性甲状腺疾病的发病机制 糖尿病倾向的BB/Wor大鼠将继续得到解决。 新 将使用免疫抑制药物（沙利度胺和环美松） 为了防止自发性碘缺乏病的发生， 在BB/Wor大鼠中诱导淋巴细胞性甲状腺炎（LT）。 这 模型也将用于确定是否，如在人类中， 短暂性肝移植在产后时期很常见。 最后， 初步的回顾性研究表明， 左旋甲状腺素治疗甲状腺功能减退症和抑制TSH 会增加骨质流失。 一项前瞻性研究 现在计划证实这些观察结果。 总体目标 这一建议的目的是提供有关约束力的进一步信息， 和外周代谢和TH的影响，并进一步 描述碘和II类（Ia）抗原在 人类和大鼠自身免疫性甲状腺疾病病因学

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.