Van Sande J, Lejeune C, Ludgate M, Munro D S, Vassart G, Dumont J E, Mockel J
Institute of Interdisciplinary Research, School of Medicine, University of Brussels, Belgium.
Mol Cell Endocrinol. 1992 Oct;88(1-3):R1-5. doi: 10.1016/0303-7207(92)90024-z.
In human thyrocytes and in a permanent CHO cell line expressing the human thyroid stimulating hormone (TSH) receptor cDNA (JP09 cells), TSH activates both the cyclic AMP and the phosphatidylinositol 4,5-bisphosphate (PIP2) cascade, although the latter effect requires higher TSH concentrations. Thyroid stimulating autoantibodies (TSAb) activate also the human thyroid leading to the hyperthyroidism of Graves' disease. They bind to the TSH receptor and mimic the TSH stimulation of the gland by increasing intracellular cyclic AMP, but they do not enhance PIP2 hydrolysis in human thyroid slices. We show in this study that TSAb are able to activate the PIP2 cascade in JP09 cells, a cell line expressing high levels of TSH receptor. This suggests that the mechanism of action of TSAb on the TSH receptor is qualitatively similar to that of TSH.
在人类甲状腺细胞以及表达人促甲状腺激素（TSH）受体cDNA的永久性中国仓鼠卵巢（CHO）细胞系（JP09细胞）中，TSH可激活环磷酸腺苷（cAMP）和磷脂酰肌醇-4,5-二磷酸（PIP2）信号通路，尽管后一种效应需要更高浓度的TSH。甲状腺刺激性自身抗体（TSAb）也可激活人类甲状腺，导致格雷夫斯病的甲状腺功能亢进。它们与TSH受体结合，并通过增加细胞内环磷酸腺苷来模拟TSH对腺体的刺激，但它们不会增强人甲状腺切片中的PIP2水解。我们在本研究中表明，TSAb能够激活JP09细胞中的PIP2信号通路，JP09细胞系表达高水平的TSH受体。这表明TSAb对TSH受体的作用机制在性质上与TSH相似。
