高胆固醇血症以及甲状腺疾病发病率日益增高，且两者经常伴随发生。长期以来，高胆固醇血症一直被认为是甲状腺功能改变的"果"，但其是否对甲状腺功能可产生影响国内外尚无报道。TTF-1是调节甲状腺激素合成重要的转录因子，可在ERK的作用下磷酸化而转变为活性形式。我们前期研究发现高胆固醇饮食大鼠甲状腺组织TTF-1表达以及血清甲状腺激素水平均明显降低,据此我们假设胆固醇可通过TTF-1介导影响甲状腺激素的合成。本研究拟采用体内（高胆固醇饮食大鼠模型、LDLR基因敲除小鼠模型）与体外实验（胆固醇刺激甲状腺细胞以及模拟正常甲状腺功能的体外重构甲状腺滤泡细胞，干扰、阻断或激活关键分子表达等手段）相结合的方式，明确高胆固醇饮食对于甲状腺功能的影响，以及胆固醇通过ERK通路抑制TTF-1磷酸化调节甲状腺激素合成的机制，提示高胆固醇饮食可能是甲状腺功能异常新的致病因素，为临床防治甲状腺疾病提供新的思路。

The incidence of thyroid diseases and hypercholesterolemia increased rapidly now. Thyroid dysfunction is often accompanied by changes in serum cholesterol level.Traditionally, hypercholesterolemia is widely considered as the result of thyroid dysfunction, but whether hypercholesterolemia also participate in the pathogenesis of thyroid dysfunction is still not very clear, and no one have take any relative investigation until now. TTF-1 is very important in the synthesis of thyroid hormone,and it can be phosphorylated and activited by ERK. Our previous found that the expression of thyroid TTF-1 and the serum thyroid hormone level decreased significantly.Therefore, we assumed that cholesterol can influence thyroid hormone synthesis mediated by TTF-1. Using both in vivo ( hypercholesterolemic rat model、LDLR knockout mouse model ) and in vitro (cholesterol stimulation on thyroid cells and reconfiguration thyroid follicular cells which can imitate normal thyroid function, interference, blocking or activation of the key molecules ) experiments,our study will verify the effect of hypercholesterolemia on thyroid function, and clarify the molecular mechanism of cholesterol on thyroid hormone synthesis through demonstrating the decreasing effect of cholesterol on TTF-1 phosphorylated mediated by ERK, further revealed a new pathogenesis mechanism for thyroid dysfunction. The project is a strong innovative research,will provide new ideas for clinical prevention and treatment of thyroid disease.