title: Iodinated TG in Thyroid Follicles Regulate TSH/TSHR Signaling for NIS Expression.
abstract: Our previous research has suggested that high degree of iodinated thyroglobulin (TG) may inhibit the expression and function of sodium iodide symporter (NIS), but the underlying mechanism remains unclear. In present study, we discuss a newly constructed follicle model in vitro, which was used to simulate the follicular structure of the thyroid and explore the regulatory roles of iodinated TG in the follicular lumen on NIS expression. The results showed that both NIS expression and PKA activity were increased in lowly iodinated TG group, while decreased NIS expression with increased PKC activity was found in highly iodinated TG group. Also, NIS expression was increased in PKA agonist-treated group, while decreased NIS was found in PKC agonist-treated group. Moreover, when the PLC-PKC pathway was blocked by PKC-specific inhibitor, highly iodinated TG significantly promoted the expression of NIS. However, when the cAMP-PKA pathway was blocked by a PKA-specific blocker, highly iodinated TG slightly suppressed NIS expression. TG with a low degree of iodination had the reverse effect on NIS. When the PLC-PKC pathway was blocked, TG with a low degree of iodination slightly promoted NIS expression. However, when the cAMP-PKA pathway was blocked, TG with a low degree of iodination greatly inhibited NIS expression. All these suggested that iodinated TG inhibited the expression of NIS by PLC-PKC pathway and promoted NIS expression via the cAMP-PKA pathway. When highly iodinated TG was present, the PLC-PKC pathway became dominant. In the presence of lowly iodinated TG, the cAMP-PKA became the major pathway.
authors.affiliation: Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou, Fujian, 362000, People's Republic of China. huibinhuang@aliyun.com.
authors.forename: Huibin
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou, Fujian, 362000, People's Republic of China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou, Fujian, 362000, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liang
authors.affiliation: Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou, Fujian, 362000, People's Republic of China.
authors.forename: Huiyao
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou, Fujian, 362000, People's Republic of China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Cai
mesh_terms: D013956:Antithyroid Agents / Q000494:pharmacology; D018929:Cell Culture Techniques; D002461:Cell Line, Transformed; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D054879:Halogenation / Q000187:drug effects; D006801:Humans; D007455:Iodine / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D008713:Methimazole / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011989:Receptors, Thyrotropin / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D027981:Symporters / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
chemical_list: D013956:Antithyroid Agents; D017868:Cyclic AMP-Dependent Protein Kinases; D020536:Enzyme Activators; D007455:Iodine; D008713:Methimazole; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D011989:Receptors, Thyrotropin; D027981:Symporters; D013954:Thyroglobulin; D013972:Thyrotropin; D000099209:Sodium-Iodide Symporters
keywords: Iodinated TG; NIS; Signaling pathway; Thyroid follicle