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

关于兔肾元节段T_4 5′-单去碘酶（5′-DI）活性的定位，我们的研究结果表明，在近曲小管和近直小管中都有活性。另一方面，在其他部分中没有检测到这些活动。此外，我们估计了5'-DI活性的亚细胞分布。这些结果表明，兔肾基底侧膜和刷状边界膜（BBM）存在高Km值5′-DI （ptu敏感），微粒体也存在高Km值5′-DI （ptu不敏感）和低Km值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脱碘到T_3是否对其对BBM磷酸盐（PI）运输的影响至关重要。从这项研究中，我们发现单独T_4可以引起BBM Pi转运的增加，并且通过5'-DI将T_4转化为T_3并不是甲状腺激素抗磷酸化作用所必需的。另一方面，我们还研究了甲状腺激素对甲状旁腺激素刺激后磷酸化的近端小管内源性蛋白的调节作用。然而，我们无法证明甲状腺激素对近端小管内源性蛋白的特异性调节作用。根据上述生物学研究数据，甲状腺激素似乎影响其在近端小管中的生理作用。因此，我们通过体外微灌注来检测甲状腺激素对近端小管的影响。与之前的研究相反，我们证明在离体正常兔小管中，近曲小管分泌钾(K)。甲状腺激素治疗24小时后，水转运和经上皮电位差无变化。这些结果表明，甲状腺激素可能不会在24小时内刺激兔近端曲小管Na-K atp酶，但净钾通量研究清楚地表明，甲状腺激素显著抑制近端曲小管中K的分泌。提示甲状腺激素可能刺激兔近曲小管基底外膜钾离子的通透性。少

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