Follicular thyroglobulin enhances gene expression necessary for thyroid hormone secretion
Follicular thyroglobulin enhances gene expression necessary for thyroid hormone secretion
复制标题
DOI：
10.1507/endocrj.ej15-0263
复制
发表时间：
2015-11-20
影响因子：
2
通讯作者：
Suzuki, Koichi
中科院分区：
文献类型：
--
作者：
Ishido, Yuko;Luo, Yuqian;Suzuki, Koichi
我们以前已经表明，滤泡甲状腺球蛋白（Tg）作为甲状腺激素（TH）生物合成的自分泌负反馈调节剂具有意想不到的功能。Tg显着抑制碘转运和TH合成所需的基因的表达，通过抵消刺激TSH。然而，滤泡Tg是否也调节细胞内TH转运和甲状腺细胞分泌尚不清楚。在本研究中，我们通过定量两种TH转运蛋白：单羧酸转运蛋白8（MCT 8）和μ-晶体蛋白（MRM）的表达来研究卵泡Tg对TH转运和分泌的潜在影响。我们的研究结果表明，在生理浓度的卵泡Tg增强大鼠甲状腺FRTL-5细胞中的MCT 8和CIMM的mRNA和蛋白表达水平的时间和剂量依赖性的方式。虽然钠/碘同向转运体（MS），碘从血液进入甲状腺的一个重要的转运体，和MCT 8，从腺体合成TH的转运体，在体内共定位于大鼠甲状腺细胞的基底外侧膜上，Tg通过抵消TSH作用降低NIS表达和增加MCT 8的表达。因此，Tg对TH分泌的影响与其先前描述的TH合成的负反馈抑制相反。我们的结果表明，Tg介导基因表达的复杂内在调节，这对于平衡两个相反的载体转运系统是必要的：新合成的TH的流入和通过外分泌的TH的流出。
We have previously shown that follicular thyroglobulin (Tg) has an unexpected function as an autocrine negative-feedback regulator of thyroid hormone (TH) biosynthesis. Tg significantly suppressed the expression of genes necessary for iodide transport and TH synthesis by counteracting stimulation by TSH. However, whether follicular Tg also regulates intracellular TH transport and its secretion from thyrocytes is not known. In the present study, we examined the potential effect of follicular Tg on TH transport and secretion by quantifying the expression of two TH transporters: monocarboxylate transporter 8 (MCT8) and mu-crystallin (CRYM). Our results showed that follicular Tg at physiologic concentrations enhanced both the mRNA and protein expression levels of MCT8 and CRYM in a time- and dose-dependent manner in rat thyroid FRTL-5 cells. Although both the sodium/iodide symporter (MS), an essential transporter of iodide from blood into the thyroid, and MCT8, a transporter of synthesized TH from the gland, were co-localized on the basolateral membrane of rat thyrocytes in vivo, Tg decreased NIS expression and increased the expression of MCT8 by counteracting TSH action. Thus, the effect of Tg on TH secretion opposed its previously described negative-feedback suppression of TH synthesis. Our results indicate that Tg mediates a complex intrinsic regulation of gene expression that is necessary to balance two opposing vectorial transport systems: the inflow of newly synthesized TH and the outflow of TH by external secretion.