A Novel Role for Thyroid-Stimulating Hormone: Up-Regulation of Hepatic 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase Expression Through the Cyclic Adenosine Monophosphate/Protein Kinase A/Cyclic Adenosine Monophosphate Responsive Element Binding Protein Pathway
A Novel Role for Thyroid-Stimulating Hormone: Up-Regulation of Hepatic 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase Expression Through the Cyclic Adenosine Monophosphate/Protein Kinase A/Cyclic Adenosine Monophosphate Responsive Element Binding Protein Pathway
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DOI：
10.1002/hep.23800
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发表时间：
2010-10-01
期刊：
影响因子：
13.5
通讯作者：
Zhao, Jiajun
中科院分区：
文献类型：
--
作者：
Tian, Limin;Song, Yongfeng;Zhao, Jiajun
促甲状腺激素（TSH）升高和高胆固醇血症通常共存，如甲状腺功能减退症中所见，但没有已知的机制直接将两者联系起来。在这里，我们证明，在肝细胞中，促甲状腺激素促进3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR），胆固醇合成的限速酶的表达，通过作用于肝细胞膜上的促甲状腺激素受体和刺激环磷酸腺苷/蛋白激酶A /环磷酸腺苷反应元件结合蛋白（cAMP/PKA/CREB）信号系统。在甲状腺切除大鼠中，通过持续给予外源性甲状腺激素抑制垂体，消除内源性甲状腺激素的产生并抑制内源性TSH，并通过给予外源性TSH增加肝脏HMGCR表达。这些结果表明，TSH可以上调肝脏HMGCR的表达，这表明一个潜在的机制，涉及TSH对肝脏的直接作用。（肝脏学2010;52：1401-1409）
Elevated thyroid-stimulating hormone (TSH) and hypercholesterolemia commonly coexist, as typically seen in hypothyroidism, but there is no known mechanism directly linking the two. Here, we demonstrated that in liver cells, TSH promoted the expression of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR), a rate-limiting enzyme in cholesterol synthesis, by acting on the TSH receptor in hepatocyte membranes and stimulating the cyclic adenosine monophosphate / protein kinase A / cyclic adenosine monophosphate responsive element binding protein (cAMP/PKA/CREB) signaling system. In thyroidectomized rats, the production of endogenous thyroid hormone was eliminated and endogenous TSH was suppressed through pituitary suppression with constant administration of exogenous thyroid hormone, and hepatic HMGCR expression was increased by administration of exogenous TSH. These results suggested that TSH could up-regulate hepatic HMGCR expression, which indicated a potential mechanism for hypercholesterolemia involving direct action of TSH on the liver. (HEPATOLOGY 2010;52:1401-1409)