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Impact of Na+/I– symporter to non-oncologic pathology of the thyroid

Dibahan Tsomartova; Elizaveta Chereshneva; Marina Ivanova; Sergey Pashin; Sergey Kuznetsov;

The Na+/I– symporter is a membrane protein implicated in iodide transport into thyroid follicular cells. The article reviews data on structure and function of Na+/I– symporter as well as transcriptional and posttranscriptional regulation of Na+/I– symporter and regulation of Na+/I– symporter expression by cytokines. The review summarizes current knowledge on implication of Na+/I– symporter in non-oncologic pathology of the thyroid like autoimmune diseases, non-thyroidal illness syndrome, and thyroid dysfunction associated with exposure to environmental pollutants like endocrine disruptors.


1. He L., Vasiliou K., Nebert D. W. Analysis and update of the human solute carrier (SLC) gene superfamily. Hum. Genomics 2009;3:195-206. https://doi.org/10.1186/1479-7364-3-2-195
2. Semenov D. Y., Boriskova M. E., Farafonova U. V., Grozov R. V., Pankova P. A. [et al.]. Prognostic value of Sodium-Iodide Symporter (NIS) in differentiated thyroid cancer. Klinicheskaya i ehksperimental’naya tireodologiya. – Clinical and experimental Thyroidology. 2015;11(1):50-58. (In Russ.). http://dx.doi.org/10.14341/ket2015150-58
3. Dzhikiya E. L., Avilov O. N., Kiseleva Ya. Yu., Kulinich T. M., Bozhenko V. K. Sodium/ iodide symporter (NIS): structure, function and role in in thyroid diseases. Vestnik Rossiyskogo nauchnogo centra Rentgenoradiologii. – Bulletin of the Russian scientific center of roentgenradiology. 2018;18(1):3. (In Russ.).
4. Portulano C., Paroder-Belenitsky M., Carrasco N. The Na+/I− Symporter (NIS): Mechanism and Medical Impact. Endocr Rev. 2014;35(1):106-149. https://doi.org/10.1210/er.2012-1036
5. Pryma D. A., Mandel S. J. Radioiodine therapy for thyroid cancer in the era of risk stratification and alternative targeted therapies. J. Nucl. Med. 2014;55(9):1485-1491. https://doi.org/10.2967/jnumed.113.131508
6. Ravera S., Reyna-Neyra A., Ferrandino G., Amzel L., Carrasco N. The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications. Annu. Rev. Physiol. 2017;79:261-289. https://doi.org/10.1146/annurev-physiol-022516-034125
7. Vunderpump M. The epidemiology of thyroid disease. Minerva Med. 2017;108(2):116-123. https://doi.org/10.23736/S0026-4806.16.04918-1
8. Dai G., Levy O., Carrasco N. Cloning and characterization of the thyroid iodide transporter. Nature. 1996;379:458- 460. https://doi.org/10.1038/379458a0
9. Darrouzet E., Lindenthal S., Marcellin D., Pellequer J.-L., Pourcher T. The sodium/iodide symporter: State of the art of its molecular characterization. Biochimica et Biophysica Acta. 2014;1838:244-253. https://doi.org/10.1016/j.bbamem.2013.08.013
10. Nicola J. P., Basquin C., Portulano C., Reyna-Neyra A., Paroder M. [et al.]. The Na+/I− symporter mediates active iodide uptake in the intestine, Am. J. Physiol. Cell Physiol. 2009;296:C654-C662. https://doi.org/10.1152/ajpcell.00509.2008
11. Paroder-Belenitsky M., Maestas M. J., Dohán O., Nicola J. P., Reyna-Neyra A. Mechanism of anion selectivity and stoichiometry of the Na+/I− symporter (NIS). PNAS. 2011;108:17933-17938. https://doi.org/10.1073/pnas.1108278108
12. Kogai T., Brent G. The sodium iodide symporter (NIS): Regulation and approaches to targeting for cancer the 370. https://doi.org/10.1016/j.pharmthera.2012.06.007
13. Carvalho D., Dupuy C. Thyroid hormone biosynthesis and release. Molecular and Cellular Endocrinology. 2017;458: 6-15. http://dx.doi.org/10.1016/j.mce.2017.01.038
14. Luo Y., Ishido Y., Hiroi N., Ishii N., Suzuki K. The emerging roles of thyroglobulin. Advances in Endocrinology. 2014. Article ID 189194. 7 pp. https://doi.org/10.3390/ijms150712895
15. Ishido Y., Yamazaki K., Kammori M., Sugishita Y., Luo Y. [et al.]. Thyroglobulin suppresses thyroid-specific gene expression in cultures of normal, but not neoplastic human thyroid follicular cells. J. Clin. Endocrinol. Metab. 2014;99(4):694-702. https://doi.org/10.1210/jc.2013-3682
16. Sellitti D. F., Suzuki K. Intrinsic Regulation of Thyroid Function by Thyroglobulin. Thyroid. 2014;24(4):625-638. https://doi.org/10.1089/thy.2013.0344
17. Pesce L., Kopp P. Iodide transport: implications for health and disease . International Journal of Pediatric Endocrinology. 2014;2014:8. Available at: http://www.ijpeonline.com/content/2014/1/8. https://doi.org/10.1186/1687-9856-2014-8
18. Yaglova N. V., Sledneva Y. P., Nazimova S. V., Obernikhin S. S. , Yaglov V. V. Sex Differences in the Production of SLC5A5, Thyroid Peroxidase, and Thyroid Hormones in Pubertal Rats Exposed to Endocrine Disruptor Dichlorodiphenyltrichloroethane (DDT) during Postnatal Ontogeny. Byulleten’ ehksperimental’noj biologii i mediciny. – Bulletin of experimental biology and medicine. 2018;164(4):430-433. (In Russ.). https://doi.org/10.1007/s10517-018-4005-1
19. Kogai T., Curcio F., Hyman S., Cornford E. M., Brent G. A., [et al.]. Induction of follicle formation in long-term cultured normal human thyroid cells treated with thyrotropin stimulates iodide uptake but not sodium/iodide symporter messenger RNA and protein expression. J. Endocrinol. 2000;167:125-135. https://doi.org/10.1677/joe.0.1670125
20. Hingorani M., Spitzweg C., Vassaugs G., Newbold K., Melcher A. [et al.]. The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery. Curr. Cancer Drug Targets. 2010;10(2):242-267. https://doi.org/10.2174/156800910791054194
21. Serrano-Nascimento C., Calil-Silveira J., Nunes M. T. Posttranscriptional regulation of sodium-iodide symporter mRNA expression in the rat thyroid gland by acute iodide administration. Am. J. Physiol. Cell. Physiol. 2010;298:C893- 899. https://doi.org/10.1152/ajpcell.00224.2009
22. Purtell K., Paroder-Belenitsky M., Reyna-Neyra A., Nicola J. P., Koba W. The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I− uptake. FASEB J. 2012;26:3252-3259. https://doi.org/ 10.1096/fj.12-206110
23. Roepke T. K., King E. C., Reyna-Neyra A., Paroder M., Purtell K. [et al.]. Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis. Nat Med. 2009;15:1186- 1194. https://doi.org/10.1038/nm.2029
24. Rapoport B., McLachlan S. Graves’ Disease: Pathogenesis and Treatment Springer Science & Business Media; 2012. 25. Alotaibi H., Tuzlakoglu-Ozturk M., Tazebay U. The Thyroid Na+/I- Symporter: molecular characterization and genomic regulation. Mol Imaging Radionucl. Ther. 2017;26(Suppl. 1):92-101. https://doi.org/10.4274/2017.26.suppl.11
26. Spitzweg C., Joba W., Morris J. C., Heufelder A. E. Regulation of sodium iodide symporter gene expression in FRTL-5 cells. Thyroid. 1999;9:821-830. https://doi.org/10.1089/thy.1999.9.821
27. Czarnocka B. Thyroperoxidase, thyroglobulin, Na(+)/I(-) symporter, pendrin in thyroid autoimmunity. Front. Biosci. (Landmark Ed). 2011;16:783-802.
28. Kucharska A. M., Czarnocka B., Demkow U. Anti-natrium/ iodide symporter antibodies and other anti-thyroid antibodies in children with Turner’s syndrome. Adv. Exp. Med. Biol. 2013;756:131-138. https://doi.org/10.1007/978-94-007-4549-0_17
29. McLachlan S., Rapoport B. Breaking Tolerance to Thyroid Antigens: Changing Concepts in Thyroid Autoimmunity. Endocrine Reviews. 2014;35:59-105. https://doi.org/10.1210/er.2013-1055
30. Yaglova N. V. Nonthyroidal illness syndrome in acute bacterial endotoxicosis: pathogenesis and method of correction. Vestnik Rossiyskoi Akademii Meditsinskikh Nauk. – Bulletin of the Russian Academy of Sciences. 2013;68(3):24-32. (In Russ.). https://doi.org/10.15690/vramn.v68i3.597
31. Yaglova N. V., Berezov T. T.Regulation of thyroid and pituitary function by bacterial lipopolysaccharide. Biomedicinskaya Khimiya. – Biomedical chemistry. 2010;56(2):179-186. (In Russ.). https://doi.org/10.18097/pbmc20105602179
32. Nicola J., Velez M., Lucero A., Fozzati L., Pellizas C. [et al.]. Functional Toll-Like Receptor 4 Conferring Lipopolysaccharide Responsiveness Is Expressed in Thyroid Cells. Endocrinology. 2009;150(1):500-508. https://doi.org/10.1210/en.2008-0345
33. Yamazaki K., Tanigawa K., Suzuki K., Yamada E., Yamada T. [et al.]. Iodide-induced chemokines and genes related to immunological function in cultured human thyroid follicles in the presence of thyrotropin. Thyroid. 2010;20(1):67-76.
34. Reale C., Zotti T., Scudiero I., Vito P., Stilo R. The NF-κB Family of Transcription Factors and Its Role in Thyroid Physiology. Vitamins and Hormones. 2018;106:195- 210. https://doi.org/10.1016/bs.vh.2017.05.003
35. Nicola J., Peyret V., Nazar M., Romero J., Lucero A. [et al.]. S-nitrosylation of NF-kB p65 inhibits TSH-induced Na+/I- symporter expression. Endocrinology. 2015;1566:4741-4754 http://dx.doi.org/10.1210/en.2015-1192
36. Nicola J., Nazar M., Mascanfroni I., Pellizas C., Masini-Repiso A. NF-kappaB p65 subunit mediates lipopolysaccharide-induced Na(+)/I(-) symporter gene expression by involving functional interaction with the paired domain transcription factor Pax8. Molecular Endocinology. 2010;24:1846-1862. https://doi.org/10.1210/me.2010-0102
37. Gore A. C., Chapell V. A., Fenton S. E., Flaws J. A., Nadal A. [et al.]. S. EDC-2: The Endocrine Sociery’s Second Scientific Statement on Endocrine Disrupting Chemicals. Endocrine Reviews. 2015;36(6):1-150. https://doi.org/ 10.1210/er.2015-1010
38. World Health Organization. 2012. State of the Science of Endocrine-Disrupting Chemicals. Geneva: International Programme on Chemical Safety.
39. Boas M., Feldt-Rasmussen U., Main K. M. Thyroid effects of endocrine disrupting chemicals. Mol. Cell. Endocrinol. 2012;355:240-248. https://doi.org/10.1016/j.mce.2011.09.005
40. Calsolaro V., Pasqualetti G., Niccolai F., Caraccio N., Monzani F. Thyroid disrupting chemicals. Int. J. Mol. Sci. 2017;18(12):25-83. Available at: www.mdpi.com/1422- 0067/18/12/2583, Accessed December 1, 2017.
41. Duntas L. H. Chemical contamination and the thyroid. Endocrine. 2015;48:53-64. https://doi.org/10.1007/s12020-014-0442-4
42. Yaglov V. V., Yaglova N. V. Alterations of thyroid morphology and function after long-term exposure to low doses of endocrine disruptor dichlorodiphenyltrichloroethane. Sovremennye Tehnologii v Medicine. – Modern technologies in medicine. 2014;6(4):55-61. (In Russ.).
43. Yaglova N. V., Yaglov V. V. Mechanisms of disruptive action of dichlorodiphenyltrichloroethane (DDT) on the function of thyroid follicular epitheliocytes. Byulleten’ ehksperimental’noj biologii i mediciny. – Bulletin of Experimental Biology and Medicine. 2015;160(2):231-233. (In Russ.). https://doi.org/10.1007/s10517-015-3136-x

Keywords: Na+/I– symporter, thyroid, cytokines, non-thyroidal illness syndrome, endocrine disruptors

Stavropol State Medical Academy
Pyatigorsk State Research Institute of Balneotherapeutics
Pyatigorsk State Pharmaceutical Academy