Iwata Tomoyuki, Yoshida Tadao, Teranishi Masaaki, Murata Yoshiharu, Hayashi Yoshitaka, Kanou Yasuhiko, Griffith Andrew J, Nakashima Tsutomu
Department of Otorhinolaryngology Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Thyroid Res. 2011 Jun 20;4(1):10. doi: 10.1186/1756-6614-4-10.
Pendred syndrome (PDS) is an autosomal recessive disorder characterized by sensorineural hearing impairment and variable degree of goitrous enlargement of the thyroid gland with a partial defect in iodine organification. The thyroid function phenotype can range from normal function to overt hypothyroidism. It is caused by loss-of-function mutations in the SLC26A4 (PDS) gene. The severity of the goiter has been postulated to depend on the amount of dietary iodine intake. However, direct evidence has not been shown to support this hypothesis. Because Slc26a4-null mice have deafness but do not develop goiter, we fed the mutant mice a control diet or an iodine-deficient diet to evaluate whether iodine deficiency is a causative environmental factor for goiter development in PDS.
We evaluated the thyroid volume in histological sections with the use of three-dimensional reconstitution software, we measured serum levels of total tri-iodothyronine (TT3) and total thyroxine (TT4) levels, and we studied the thyroid gland morphology by transmission electron microscopy.
TT4 levels became low but TT3 levels did not change significantly after eight weeks of an iodine-deficient diet compared to levels in the control diet animals. Even in Slc26a4-null mice fed an iodine-deficient diet, the volume of the thyroid gland did not increase although the size of each epithelial cell increased with a concomitant decrease of thyroid colloidal area.
An iodine-deficient diet did not induce goiter in Slc26a4-null mice, suggesting that other environmental, epigenetic or genetic factors are involved in goiter development in PDS.
Pendred综合征（PDS）是一种常染色体隐性疾病，其特征为感音神经性听力障碍以及甲状腺不同程度的肿大，伴有碘有机化部分缺陷。甲状腺功能表型范围可从正常功能到明显的甲状腺功能减退。它由SLC26A4（PDS）基因突变导致功能丧失引起。甲状腺肿的严重程度据推测取决于饮食中碘的摄入量。然而，尚无直接证据支持这一假说。由于Slc26a4基因敲除小鼠存在耳聋但未出现甲状腺肿，我们给突变小鼠喂食对照饮食或缺碘饮食，以评估碘缺乏是否是PDS中甲状腺肿发生的环境致病因素。
我们使用三维重建软件评估组织切片中的甲状腺体积，测量血清总三碘甲状腺原氨酸（TT3）和总甲状腺素（TT4）水平，并通过透射电子显微镜研究甲状腺形态。
与喂食对照饮食的动物相比，缺碘饮食八周后TT4水平降低，但TT3水平无显著变化。即使在喂食缺碘饮食的Slc26a4基因敲除小鼠中，甲状腺体积也未增加，尽管每个上皮细胞大小增加，同时甲状腺胶体区域减小。
缺碘饮食未在Slc26a4基因敲除小鼠中诱发甲状腺肿，提示其他环境、表观遗传或遗传因素参与了PDS中甲状腺肿的发生。
