Szinnai Gabor, Lacroix Ludovic, Carré Aurore, Guimiot Fabien, Talbot Monique, Martinovic Jelena, Delezoide Anne-Lise, Vekemans Michel, Michiels Stefan, Caillou Bernard, Schlumberger Martin, Bidart Jean-Michel, Polak Michel
Faculty of Medicine René Descartes, Paris V, Site Necker, Institut National de la Santé et de la Recherche Médicale Equipe Mixte 0363, Pediatric Endocrine Unit, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Paris, France.
J Clin Endocrinol Metab. 2007 Jan;92(1):70-6. doi: 10.1210/jc.2006-1450. Epub 2006 Oct 31.
Terminal differentiation of the human thyroid is characterized by the onset of follicle formation and thyroid hormone synthesis at 11 gestational weeks (GW).
This study aimed to investigate the ontogeny of thyroglobulin (Tg), thyroid peroxidase (TPO), sodium/iodide symporter (NIS), pendrin (PDS), dual oxidase 2 (DUOX2), thyroid-stimulating hormone receptor (TSHR), and thyroid transcription factor 1 (TITF1), forkhead box E1 (FOXE1), and paired box gene 8 (PAX8) in the developing human thyroid.
Thyroid tissues from human embryos and fetuses (7-33 GW; n = 45) were analyzed by quantitative PCR to monitor mRNA expression for each gene and by immunohistochemistry to determine the cellular distribution of TITF1, TSHR, Tg, TPO, NIS, and the onset of T4 production. A broken line regression model was fitted for each gene to compare the loglinear increase in expression before and after the onset of T4 synthesis.
TITF1, FOXE1, PAX8, TSHR, and DUOX2 were stably expressed from 7 to 33 GW. Tg, TPO, and PDS expression was detectable as early as 7 GW and was correlated with gestational age (all, P < 0.01), and the slope of the regression line was significantly different before and after the onset of T4 synthesis at 11 GW (all, P < 0.01). NIS expression appeared last and showed the highest fit by the broken line regression model of all genes (correlation age P < 0.0001, broken line regression P < 0.0001). Immunohistochemical studies detected TITF1, TSHR, and Tg in unpolarized thyrocytes before follicle formation. T(4) and NIS labeling were only found in developing follicles from 11 GW on.
These results imply a key role of NIS for the onset of human thyroid function.
人类甲状腺的终末分化特征为在妊娠11周（GW）时开始形成滤泡并合成甲状腺激素。
本研究旨在调查甲状腺球蛋白（Tg）、甲状腺过氧化物酶（TPO）、钠/碘同向转运体（NIS）、pendrin（PDS）、双氧化酶2（DUOX2）、促甲状腺激素受体（TSHR）以及甲状腺转录因子1（TITF1）、叉头框E1（FOXE1）和配对盒基因8（PAX8）在发育中的人类甲状腺中的个体发生情况。
对来自人类胚胎和胎儿（7 - 33 GW；n = 45）的甲状腺组织进行定量PCR分析，以监测每个基因的mRNA表达，并通过免疫组织化学确定TITF1、TSHR、Tg、TPO、NIS的细胞分布以及T4产生的起始情况。对每个基因拟合折线回归模型，以比较T4合成开始前后表达的对数线性增加。
TITF1、FOXE1、PAX8、TSHR和DUOX2在7至33 GW期间稳定表达。Tg、TPO和PDS的表达早在7 GW时就可检测到，且与胎龄相关（均P < 0.01），在11 GW T4合成开始前后，回归线的斜率有显著差异（均P < 0.01）。NIS表达出现最晚，且在所有基因的折线回归模型中拟合度最高（相关年龄P < 0.0001，折线回归P < 0.0001）。免疫组织化学研究在滤泡形成前未极化的甲状腺细胞中检测到TITF1、TSHR和Tg。从11 GW起，仅在发育中的滤泡中发现T(4)和NIS标记。
这些结果表明NIS在人类甲状腺功能起始中起关键作用。
