Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland.
Department of Pediatrics, Turku University Hospital, Kiinamyllynkatu 4-8, 20521, Turku, Finland.
Best Pract Res Clin Endocrinol Metab. 2018 Jun;32(3):241-256. doi: 10.1016/j.beem.2018.03.007. Epub 2018 Apr 3.
The thyroid gland produces thyroid hormones (TH), which are essential regulators for growth, development and metabolism. The thyroid is mainly controlled by the thyroid-stimulating hormone (TSH) that binds to its receptor (TSHR) on thyrocytes and mediates its action via different G protein-mediated signaling pathways. TSH primarily activates the G-pathway, and at higher concentrations also the G-pathway, leading to an increase of intracellular cAMP and Ca, respectively. To date, the physiological importance of other G protein-mediated signaling pathways in thyrocytes is unclear. Congenital hypothyroidism (CH) is defined as the lack of TH at birth. In familial cases, high-throughput sequencing methods have facilitated the identification of novel mutations. Nevertheless, the precise etiology of CH yet remains unraveled in a proportion of cases. Genetically modified mouse models can reveal new pathophysiological mechanisms of thyroid diseases. Here, we will present an overview of genetic mouse models for thyroid diseases, which have provided crucial insights into thyroid gland development, function, and growth with a special focus on TSHR and microRNA signaling.
甲状腺产生甲状腺激素（TH），这些激素是生长、发育和代谢所必需的调节剂。甲状腺主要受甲状腺刺激激素（TSH）的控制，TSH 与甲状腺细胞上的受体（TSHR）结合，并通过不同的 G 蛋白介导的信号通路介导其作用。TSH 主要激活 G 通路，在更高浓度下也激活 G 通路，分别导致细胞内 cAMP 和 Ca 的增加。迄今为止，G 蛋白介导的信号通路在甲状腺细胞中的生理重要性尚不清楚。先天性甲状腺功能减退症（CH）定义为出生时缺乏 TH。在家族性病例中，高通量测序方法促进了新突变的鉴定。然而，在一部分病例中，CH 的精确病因仍未阐明。基因修饰的小鼠模型可以揭示甲状腺疾病的新病理生理机制。在这里，我们将介绍甲状腺疾病的基因小鼠模型概述，这些模型为甲状腺发育、功能和生长提供了重要的见解，特别关注 TSHR 和 microRNA 信号。
