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 Bernier-Valentin, F. Articles by Rousset, B. Search for Related Content PubMed PubMed Citation Articles by Bernier-Valentin, F. Articles by Rousset, B. Pubmed/NCBI databases Substance via MeSH

Three-Dimensional Organization of Thyroid Cells into Follicle Structures Is a Pivotal Factor in the Control of Sodium/Iodide Symporter Expression

Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 369, F-69372 Lyon, France; Faculté de Médecine Laennec, F-69372 Lyon, France; and Université Lyon, F-69200 Lyon, France

Address all correspondence and requests for reprints to: Dr. Bernard Rousset, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 369, Faculté de Médecine Laennec, 7 rue Guillaume Paradin, 69372 Lyon Cedex 08, France. E-mail: u369{at}sante.univ-lyon1.fr.

Expression of sodium/iodide symporter (NIS) by thyroid epithelial cells is primarily regulated by TSH, which acts at the level of NIS gene transcription. Knowledge of the mechanisms governing NIS expression mainly comes from studies of rat thyroid-derived cell lines forming cell monolayers. In this study we investigated the impact of the three-dimensional organization of thyroid cells into follicles on the regulation of NIS expression. We used porcine thyrocytes in primary culture that, depending on cell density and the moment TSH is added, either predominantly form a cell monolayer (CM) or reconstitute thyroid follicles (RTF). NIS expression analyzed at transcript and protein levels was remarkably high in RTF compared with CM. Cells forming RTF were NIS positive, whereas in CM, NIS was only detected in the limited number of cells forming follicle-like structures. When thyrocytes were cultured at increasing cell density to obtain a gradual shift from CM to RTF, the progressive increase in the proportion of cells enrolled in RTF was accompanied by a parallel increase in NIS expression. Other TSH-regulated genes, thyroperoxidase, Na⁺,K⁺-adenosine triphosphatase -subunit, and thyroglobulin, were expressed at similar levels whatever the organization of thyrocytes in culture. The transcription factor, Pax-8, was equally expressed in NIS-negative CM and NIS-positive RTF. We show that TSH highly activates NIS expression only when thyrocytes have undergone histiotypic morphogenesis. This finding suggests that TSH activation of NIS gene transcription might involve, in addition to Pax-8, a regulatory factor(s) whose synthesis and/or activity are triggered by cell-cell interaction(s) occurring in the course of folliculogenesis.

This article has been cited by other articles:

				G. Szinnai, L. Lacroix, A. Carre, F. Guimiot, M. Talbot, J. Martinovic, A.-L. Delezoide, M. Vekemans, S. Michiels, B. Caillou, et al. Sodium/Iodide Symporter (NIS) Gene Expression Is the Limiting Step for the Onset of Thyroid Function in the Human Fetus J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 70 - 76. [Abstract] [Full Text] [PDF]

				T Kogai, K Taki, and G A Brent Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. Endocr. Relat. Cancer, September 1, 2006; 13(3): 797 - 826. [Abstract] [Full Text] [PDF]