Bernier-Valentin Françoise, Trouttet-Masson Séverine, Rabilloud Rachida, Selmi-Ruby Samia, Rousset Bernard
Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 369, Faculté de Médecine Laennec, Lyon, France.
Endocrinology. 2006 Apr;147(4):2035-42. doi: 10.1210/en.2005-0805. Epub 2005 Dec 8.
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 alpha-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.
甲状腺上皮细胞钠/碘同向转运体（NIS）的表达主要受促甲状腺激素（TSH）调控，TSH作用于NIS基因转录水平。关于NIS表达调控机制的认识主要来自对形成细胞单层的大鼠甲状腺来源细胞系的研究。在本研究中，我们探究了甲状腺细胞形成滤泡的三维结构对NIS表达调控的影响。我们使用原代培养的猪甲状腺细胞，根据细胞密度和添加TSH的时间，这些细胞要么主要形成细胞单层（CM），要么重新构建甲状腺滤泡（RTF）。与CM相比，在转录和蛋白质水平分析的NIS表达在RTF中显著更高。形成RTF的细胞NIS呈阳性，而在CM中，仅在形成滤泡样结构的有限数量细胞中检测到NIS。当甲状腺细胞以增加的细胞密度培养以获得从CM到RTF的逐渐转变时，参与RTF的细胞比例的逐渐增加伴随着NIS表达的平行增加。无论培养中甲状腺细胞的组织结构如何，其他受TSH调控的基因，甲状腺过氧化物酶、钠钾ATP酶α亚基和甲状腺球蛋白，均以相似水平表达。转录因子Pax - 8在NIS阴性的CM和NIS阳性的RTF中表达水平相同。我们发现，只有当甲状腺细胞经历组织形态发生时，TSH才会高度激活NIS表达。这一发现表明，除了Pax - 8之外，TSH对NIS基因转录的激活可能还涉及一种调控因子，其合成和/或活性由滤泡发生过程中发生的细胞间相互作用触发。
