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离散甲状腺细胞甲状腺素合成细胞内途径的鉴定

Identification of an intracellular pathway of thyroxine synthesis by dispersed thyroid cells.

作者信息

Rousset B, Mornex R

出版信息

Biochim Biophys Acta. 1981 Aug 5;676(1):8-18. doi: 10.1016/0304-4165(81)90003-9.

DOI:10.1016/0304-4165(81)90003-9
PMID:7260113
Abstract

This study deals with the identification of the biochemical events involved in the metabolic sequence leading from the synthesis to the release of thyroxine in the dispersed thyroid cell system. (1) Using an experimental model allowing the differentiation between intracellular and extracellular sites of iodination, it is shown that thyroxine is synthesized inside the cells by an iodinating system sensitive to thyrotropin stimulation. (2) The secretion of thyroxine synthesized inside the cells is not mediated by an exocytotic-endocytotic phenomenon. Colchicine, vinblastine, fluoride, propanolol and chlorpromazine, at concentrations equal to or 10--100-times higher than those required to inhibit hormone release in follicular-organized thyroid tissue have no effect on thyrotropin-stimulated thyroxine secretion. (3) The secretion involves the intracellular proteolysis of hormone-containing iodoprotein(s) which, in addition to free thyroxine, generates free mono- and diiodotyrosines. Free thyroxine is released into the incubation medium and iodotyrosines are deiodinated under normal conditions and accumulate in the presence of an inhibitor of iodotyrosine deiodinase: 3,5-dinitrotyrosine. This proteolysis is inhibited by 5 mM chlorpromazine. These data indicate that the complete metabolic sequence leading from the uptake of iodide to the release of free thyroxine into the incubation medium can be described as an 'intracellular metabolic sequence for thyroxine synthesis'.

摘要

本研究旨在确定在离散甲状腺细胞系统中,从甲状腺素合成到释放的代谢序列中所涉及的生化事件。(1) 使用一种能区分碘化细胞内和细胞外位点的实验模型,结果表明甲状腺素是在细胞内由对促甲状腺素刺激敏感的碘化系统合成的。(2) 细胞内合成的甲状腺素的分泌不是由胞吐 - 胞吞现象介导的。秋水仙碱、长春花碱、氟化物、普萘洛尔和氯丙嗪,其浓度等于或比抑制滤泡状甲状腺组织中激素释放所需浓度高10 - 100倍,对促甲状腺素刺激的甲状腺素分泌没有影响。(3) 分泌涉及含激素的碘蛋白的细胞内蛋白水解,除了游离甲状腺素外,还产生游离的单碘酪氨酸和二碘酪氨酸。游离甲状腺素释放到培养液中,碘酪氨酸在正常情况下脱碘,并在碘酪氨酸脱碘酶抑制剂:3,5 - 二硝基酪氨酸存在时积累。这种蛋白水解被5 mM氯丙嗪抑制。这些数据表明,从碘摄取到游离甲状腺素释放到培养液中的完整代谢序列可被描述为“甲状腺素合成的细胞内代谢序列”。

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