Sellitti Donald F, Suzuki Koichi
1 Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland.
Thyroid. 2014 Apr;24(4):625-38. doi: 10.1089/thy.2013.0344. Epub 2014 Jan 17.
The established paradigm for thyroglobulin (Tg) function is that of a high molecular weight precursor of the much smaller thyroid hormones, triiodothyronine (T3) and thyroxine (T4). However, speculation regarding the cause of the functional and morphologic heterogeneity of the follicles that make up the thyroid gland has given rise to the proposition that Tg is not only a precursor of thyroid hormones, but that it also functions as an important signal molecule in regulating thyroid hormone biosynthesis.
Evidence supporting this alternative paradigm of Tg function, including the up- or downregulation by colloidal Tg of the transcription of Tg, iodide transporters, and enzymes employed in Tg iodination, and also the effects of Tg on the proliferation of thyroid and nonthyroid cells, is examined in the present review. Also discussed in detail are potential mechanisms of Tg signaling in follicular cells.
Finally, we propose a mechanism, based on experimental observations of Tg effects on thyroid cell behavior, that could account for the phenomenon of follicular heterogeneity as a highly regulated cycle of increasing and decreasing colloidal Tg concentration that functions to optimize thyroid hormone production through the transcriptional activation or suppression of specific genes.
甲状腺球蛋白（Tg）功能的既定模式是作为分子量比其小得多的甲状腺激素——三碘甲状腺原氨酸（T3）和甲状腺素（T4）的高分子量前体。然而，关于构成甲状腺的滤泡在功能和形态上存在异质性的原因的推测引发了这样一种观点，即Tg不仅是甲状腺激素的前体，而且在调节甲状腺激素生物合成中还作为一种重要的信号分子发挥作用。
本综述考察了支持Tg功能这一替代模式的证据，包括胶体Tg对Tg转录、碘转运体以及参与Tg碘化的酶的上调或下调作用，以及Tg对甲状腺细胞和非甲状腺细胞增殖的影响。还详细讨论了滤泡细胞中Tg信号传导的潜在机制。
最后，基于对Tg对甲状腺细胞行为影响的实验观察结果，我们提出一种机制，该机制可以解释滤泡异质性现象是一个高度调节的胶体Tg浓度增减循环，其作用是通过特定基因的转录激活或抑制来优化甲状腺激素的产生。
