RENAL THYROID HORMONE UPTAKE AND DEIODINATION

肾甲状腺激素的摄取和脱碘

• 批准号: 3447619
• 负责人: DUNCAN C FERGUSON
• 金额: $ 5.09万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3447619
• 关键词: chromatography; hormone metabolism; hormone regulation /control mechanism; iodination; iodine; kidney function; membrane permeability; perfusion; radioimmunoassay; triiodothyronine

The long term objective of this proposal is to study the factors which regulate the peripheral tissue uptake of thyroxine (T4), the main secretory product of the thyroid gland, and subsequent 5'-deiodination to 3,5,3'-triiodothyronine (T3), the most potent thyroid hormone, and 5-deiodination to 3,3',5' triiodothyronine (rT3), a thyromimetically inactive product. Specifically, emphasis will be placed on the role of the kidney in the whole body production of T3. Using an established method of kidney perfusion, as well as plasma membrane preparations, the mechanisms of renal uptake and deiodination of T4 and T3 will be characterized. The locus of deiodination will be functionally identified relative to the site of tubular iodide handling in the perfused kidney. Measurements of thyroid hormone metabolites will be accomplished both with radioimmunoassay techniques and with high pressure liquid chromatographic (HPLC) analysis of radioactive tracer compounds. The perfused organ system provides the opportunity to study thyroid hormone metabolism in an intact organ which is separation from the confounding effects of other tissues. In addition, the perfused organ is potentially able to respond to hormonal and substrate stimuli. The mechanisms regulating the decreased renal production during diabetes mellitus will be further explored. In addition, the perfused kidney's production and degradation of rT3 will be compared with its T3 production. The effect of membrane-stabilizing drugs and organic anions on thyroid hormone uptake and metabolism will be examined. Rates of influx and efflux of thyroid hormone will be used to characterize changes in the renal retention of these compounds. Cytosolic-binding will be correlated with changes in organ uptake of iodothyronines after alterations in metabolic state and therapy with certain drugs. Preparations of luminal and contraluminal renal plasma membrane vesicles will be used to study the relative 5'-deiodination rates at these sites as well as to explore the existence of membrane transport systems for iodothyronines and iodide. These studies will contribute to the understanding of individual organ thyroid hormone uptake and metabolism, its relation to thyroid hormone action, and potential steps at which thyromimetic activity may be modified at the cellular level.

该提案的长期目标是研究影响因素 调节外周组织对甲状腺素（T4）的摄取，甲状腺素是主要的分泌物质 甲状腺产物，随后 5'-脱碘 3,5,3'-三碘甲状腺原氨酸 (T3)，最有效的甲状腺激素，以及 5-脱碘为 3,3',5' 三碘甲状腺原氨酸 (rT3)，一种拟甲状腺素 不活跃的产品。 具体而言，将重点强调 肾脏在全身产生T3。 使用既定的肾脏灌注方法以及质膜 制剂、T4和T3的肾脏摄取和脱碘机制 将被表征。 脱碘位点将在功能上 相对于灌注管中管状碘化物处理的位置进行识别 肾。 将完成甲状腺激素代谢物的测量 均采用放射免疫分析技术和高压液体 放射性示踪剂化合物的色谱（HPLC）分析。 这 灌注器官系统提供了研究甲状腺激素的机会 完整器官中的新陈代谢，与混杂因素分离 其他组织的影响。 此外，灌注器官可能 能够对激素和底物刺激做出反应。 糖尿病期间肾脏生成减少的调节机制 将进一步探讨。 此外，灌注肾 rT3 的产生和降解将与其 T3 产生进行比较。 膜稳定药物和有机阴离子对甲状腺的影响 将检查激素摄取和代谢。 流入率和流出率 甲状腺激素的变化将被用来表征肾功能的变化 保留这些化合物。 胞质结合将与 代谢改变后器官对碘甲状腺原氨酸的摄取发生变化 状态和某些药物的治疗。 鲁米那制剂和 腔内肾质膜囊泡将用于研究 这些位点的相对 5'-脱碘率以及探索 碘甲状腺原氨酸和碘化物的膜转运系统的存在。 这些研究将有助于了解个体器官 甲状腺激素的摄取和代谢及其与甲状腺激素的关系 可能改变拟甲状腺活性的行动和潜在步骤 在细胞水平上。