This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Suzuki, K. Articles by Kohn, L. D. Search for Related Content PubMed PubMed Citation Articles by Suzuki, K. Articles by Kohn, L. D. Pubmed/NCBI databases Substance via MeSH Hazardous Substances DB THYROGLOBULIN

Follicular Thyroglobulin Suppresses Iodide Uptake by Suppressing Expression of the Sodium/Iodide Symporter Gene

Cell Regulation Section, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Dr. Leonard D. Kohn, Cell Regulation Section, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Building 10, Room 9C101B, National Institutes of Health, Bethesda, Maryland 20892-1800. E-mail: lenk{at}bdg10.niddk.nih.gov

A major function of the thyrocyte is to take up and concentrate iodide. This is needed for thyroid hormone synthesis and is accomplished by the sodium iodide symporter (NIS), whose expression and activity are up-regulated by TSH. Recently, we reported that follicular thyroglobulin (TG) is a potent suppressor of thyroid-specific gene expression and can overcome TSH-increased gene expression. We suggested this might be a negative feedback, autoregulatory mechanism that counterbalanced TSH stimulation of follicular function. In this report, we support this hypothesis by coordinately evaluating TG regulation of NIS gene expression and iodide transport. We show that physiological concentrations of TG similarly and significantly suppress TSH-increased NIS promoter activity, NIS protein, and NIS-dependent iodide uptake as well as RNA levels. We show, in vivo, that TG accumulation at the apical membrane of a thyrocyte facing the follicular lumen is associated with decreased uptake of radioiodide. It is likely, therefore, that TG suppresses NIS-dependent iodide uptake and NIS gene expression in vivo, as is the case in vitro. RNA levels of NIS and vascular endothelial growth factor/vascular permeability factor, which has been reported to be TSH regulated and possibly associated with TSH-increased iodide uptake, are coordinately decreased by follicular TG as a function of concentration and time. Also, removal of follicular TG from the medium, but not TSH, coordinately returns NIS and vascular endothelial growth factor/vascular permeability factor RNA levels to their TSH-stimulated state. TG accumulated in the follicular lumen appears, therefore, to be a negative feedback regulator of critical TSH-increased follicular functions, iodide uptake, and vascular permeability.

This article has been cited by other articles:

				G. Riesco-Eizaguirre and P. Santisteban A perspective view of sodium iodide symporter research and its clinical implications. Eur. J. Endocrinol., October 1, 2006; 155(4): 495 - 512. [Abstract] [Full Text] [PDF]

				K. Suzuki and L. D Kohn Differential regulation of apical and basal iodide transporters in the thyroid by thyroglobulin. J. Endocrinol., May 1, 2006; 189(2): 247 - 255. [Abstract] [Full Text] [PDF]

				O. Dohan, A. De la Vieja, V. Paroder, C. Riedel, M. Artani, M. Reed, C. S. Ginter, and N. Carrasco The Sodium/Iodide Symporter (NIS): Characterization, Regulation, and Medical Significance Endocr. Rev., February 1, 2003; 24(1): 48 - 77. [Abstract] [Full Text] [PDF]

				A. Yoshida, S. Taniguchi, I. Hisatome, I. E. Royaux, E. D. Green, L. D. Kohn, and K. Suzuki Pendrin Is an Iodide-Specific Apical Porter Responsible for Iodide Efflux from Thyroid Cells J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3356 - 3361. [Abstract] [Full Text] [PDF]

				M. Nakazato, H.-K. Chung, L. Ulianich, A. Grassadonia, K. Suzuki, and L. D. Kohn Thyroglobulin Repression of Thyroid Transcription Factor 1 (TTF-1) Gene Expression Is Mediated by Decreased DNA Binding of Nuclear Factor I Proteins Which Control Constitutive TTF-1 Expression Mol. Cell. Biol., November 15, 2000; 20(22): 8499 - 8512. [Abstract] [Full Text]

				M. Marino and R. T. McCluskey Role of thyroglobulin endocytic pathways in the control of thyroid hormone release Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1295 - C1306. [Abstract] [Full Text] [PDF]