Physiological role of the conversion of T_4 to T_3 and its relationship to phosphorelation in the kidney.

T_4 转化为 T_3 的生理作用及其与肾脏磷酸化的关系。

• 批准号: 61570316
• 负责人: ASANO Yasushi
• 金额: $ 1.41万
• 依托单位: Jichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570316/
• 关键词: Thyroid hormone; Kidney; T_4.5'-monodeiodinase activity; K-secretion; 蛋白リン酸化; 甲状腺ホルモン、ナトリウム依存性リン輸送; 甲状腺ホルモン; 近位尿細管リン輸送; 近位尿細管カリウム輸送; ナトリウム依存性リン輸送; 近位曲尿細管; サイトゾール; 副甲状腺ホルモン; c-AMP

Concerning the localization of T_4 5'-monodeiodinase (5'-DI) activity in rabbit nephron segments, our results indicated that the activities were noted in both proximal convoluted and proximal straight tubules. On the other hand, the activities were not detected in other segments. In addition, we estimated the subcellular distribution of 5'-DI activity. These results indicated that there exists high Km valued 5'-DI (PTU-sensitive) at basolateral membrane and brush border membrane (BBM) and also exists high Km and low Km valued 5'-DI (PTU-insensitive) at microsome in the rabbit kidney. Since 5'-DI is localized exclusively in proximal tubules, we examined whether T_4 deiodination to T_3 is essential for its effect on BBM phosphate (PI) transport. From this study, we showed that T_4 alone can cause the increase in BBM Pi transport and that intrarenal T_4 conversion to T_3 by 5'-DI is not essential for antiphosphaturic effect of thyroid hormones. On the other hand, we also investigated the … More modulatory effect of thyroid hormone on endogenous proteins in proximal tubules which are phosphorylated after parathyroid hormone stimulation. However, we could not demonstrated specific modulatory effect of thyroid hormone on these endogenous proteins in proximal tubules. According to the data obtained from biological studies mentioned above, thyroid hormones seems to affect its physiological action in the proximal tubules. Thus we examined the effect of thyroid hormones in the proximal tubules by in vitro microperfusion. In contrast to the previous study, we demonstrated that in the proximal convoluted tubules, potassium (K) was secreted in normal rabbit tubules in vitro. 24 hours after the treatment of thyroid hormones water transport and transepithelial potential difference showed no change. These findings indicated that thyroid hormones might not stimulate Na-K ATPase in rabbit rpoximal convoluted tubules in 24 hours, however, net potassium flux studies clearly indicated that thyroid hormones significantly suppressed K secretion in proximal convoluted tubules. These findings suggests thyroid hormone may stimulate the K permeability in the basolateral membrane of rabbit proximal convoluted tubules. Less

关于T_4 5 ′-单脱碘酶（5 ′-DI）活性在兔肾单位节段的定位，我们的结果表明，在近曲小管和近直小管中均观察到这种活性。另一方面，在其他部门没有发现这些活动。此外，我们估计了5 '-DI活性的亚细胞分布。结果表明，兔肾基底外侧膜和刷状缘膜（BBM）存在高Km值的5 ′-DI（PTU敏感），微粒体存在高Km值和低Km值的5 ′-DI（PTU不敏感）。由于5 '-DI仅定位于近端小管，我们研究了T_4脱碘为T_3是否是其影响BBM磷酸盐（PI）转运的必要条件。本研究表明，T_4可引起BBM Pi转运增加，5 ′-DI在肾内将T_4转化为T_3不是甲状腺激素抗磷酸尿作用所必需的。另一方面，我们也调查了 ...更多信息 甲状腺激素对近端小管内源性蛋白质的调节作用，这些蛋白质在甲状旁腺激素刺激后被磷酸化。然而，我们不能证明甲状腺激素对这些内源性蛋白在近端小管的特异性调节作用。根据上述生物学研究获得的数据，甲状腺激素似乎影响其在近端小管中的生理作用。因此，我们研究了甲状腺激素在近端小管的影响，在体外微灌注。与以前的研究相反，我们证明，在近曲小管，钾（K）分泌在正常兔肾小管在体外。治疗后24 h甲状腺激素水转运及跨上皮电位差无变化。结果表明，甲状腺激素在24小时内对近曲小管Na-K ATP酶无刺激作用，而钾净流量研究表明甲状腺激素显著抑制近曲小管K分泌。提示甲状腺激素可刺激家兔近曲小管基底外侧膜钾离子通透性。少