IODINE METABOLISM OF THE THYROID GLAND

甲状腺的碘代谢

• 批准号: 3224371
• 负责人: ISADORE N. ROSENBERG
• 金额: $ 23.78万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1975
• 资助国家: 美国
• 起止时间: 1975-09-01 至 1990-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3224371
• 关键词: 3'5' cyclic nucleotide phosphodiesterase; adenosinetriphosphatase; adenylate cyclase; calcium transporting ATPase; chromatography; cyclic AMP; cyclic GMP; electrofocusing; electron transport; enzyme mechanism; flavoproteins; gel electrophoresis; hormone biosynthesis; hormone metabolism; human tissue; hyperthyroidism; hypothyroidism; iodination; iodotyrosine; laboratory rabbit; laboratory rat; radioimmunoassay; radiotracer; spectrometry; thiols; thiouracil; thyroid function; thyroid hormone binding protein; thyrotropin; tissue /cell culture; triiodothyronine

This is a proposal to investigate some aspects of iodine and thyroid hormone metabolism and will focus on (I) the mechanism(s) and biochemical and physiological regulation of thyroid hormone deiodination in rat tissues, with emphasis on the formation of T3 from T4, (II) identification and characterization of the thiol cofactor mechanism responsible for the activation of thyroid hormone deiodination in vivo, (III) roles of cAMP and cGMP in the espression of thyroid hormone action at the cellular level, and (IV) characterization of a thyroaidal electron-transfer system in relation to the NADPH-dependent deiodination of iodotyrosines. Goal (I) will be approached by attempts at solubilization, purification and kinetic characterization of the 'high' and 'low' Km iodothyronine 5'-deiodinases in various tissues as well as by in vivo studies aimed at assessing their relative contribution to circulating T3 in various thyroid states. Goal (II) will characterize (a) the cytosolic thiol protein that promotes GSH-activation of iodothyronine 5'-deiodinases in vitro, and examine its relationship to glutaredoxin, and (b) another soluble thiol protein which catalyzes oxidative degradation of iodothyronines and evaluate its possible role as a disposal mechanism for excess iodothyronines. Goal (III) will examine the effects of thyroid status on the enzymatic properties, molecular forms and dynamic interrelationships of cAMP- and cGMP-phosphodiesterases in adipocytes and their concerted effects on the steady state levels of cellular cAMP and cGMP. Goal (IV) will be pursued experimentally by purification of thyroid ferredoxin and NADPH-ferredoxin reductase, establishment of its role in deiodination of iodotyrosines and characterization of the enzymatic and molecular properties of the reductase enzyme in relation to protease-purified preparations of thyroid iodotyrosine deiodinase.

这是研究碘和甲状腺的某些方面的建议 激素代谢，并将重点放在（i）机制和生化 大鼠甲状腺激素去牙的生理调节 组织，重点是T4的T3形成，（ii）鉴定 以及负责硫醇辅因子机制的表征 甲状腺激素在体内的激活，cAMP和CAMP的作用（III） CGMP在甲状腺激素作用在细胞水平上的刺激中，并且 （iv）与关系的甲状腺电子转移系统的表征 依赖于NADPH的碘酪氨酸去化。 目标（i）将是 通过尝试溶解，纯化和动力学来接近 “高”和“低”碘甲糖氨酸5'-二二酶的特征 各种组织以及体内研究旨在评估其 在甲状腺各种状态下对循环T3的相对贡献。 目标 （ii）将表征（a）促进的胞质硫醇蛋白 在体外对碘甲氧氨酸5'-二二氨酸酶的GSH激活，并检查其 与谷化毒素的关系，（b）另一种可溶性硫醇蛋白 催化碘甲醇的氧化降解并评估其可能 作为过量碘甲醇的处置机制的作用。 目标（iii）将 检查甲状腺状态对酶特性的影响， cAMP和CAMP的分子形式和动态相互关系 脂肪细胞中的CGMP磷酸二酯酶及其对脂肪细胞的一致影响 细胞营和CGMP的稳态水平。 目标（iv）将被追求 通过纯化甲状腺铁氧还蛋白和NADPH-铁毒素的纯化实验 还原酶，建立其在碘化碘化中的作用和 还原酶的酶促和分子特性的表征 与甲状腺的蛋白酶纯制剂有关的酶 碘酪氨酸去二世酶。