Huber G K, Safirstein R, Neufeld D, Davies T F
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
J Clin Endocrinol Metab. 1991 May;72(5):1142-7. doi: 10.1210/jcem-72-5-1142.
Graves' disease encompasses hyperthyroidism and a diffuse goiter associated with autoantibodies to the TSH receptor (TRAb). Although the cause of the goiter formation has been attributed to TRAb, the limited growth pattern of human adult thyroid cells in vitro has caused such a conclusion to be based on studies of nonhuman thyroid cell growth. We have recently characterized a predictable and precise technique for the measurement of human thyroid cell proliferation and function using fetal thyroid cells and have used this system to examine the influence of TRAb on human thyroid cell growth. Highly purified human immunoglobulin G (hIgG) preparations from normal individuals (n = 5) had no significant influence on human thyroid cell growth. However, hIgG from patients with detectable TRAb (TRAb-hIgG) (n = 13) induced a dose-related increase in extracellular cAMP (maximum effect at 0.1 mg/ml) and a 3-fold increase in human thyroid cell growth over a 4-day period (maximum effect at 1.5 mg/ml). Under basal thyroid cell culture conditions there were detectable, but low, levels of mRNA specific for the protooncogene c-fos, and this was markedly, and rapidly, induced by the addition of TRAb-hIgG but not normal hIgG. These data demonstrate induction of cellular growth by TRAb-hIgG in an homologous human thyroid cell culture system. Such observations support the hypothesis that goiter formation in patients with Graves' disease is, at least in part, secondary to the growth stimulating activity of TRAb-hIgG.
格雷夫斯病包括甲状腺功能亢进以及与促甲状腺激素受体自身抗体（TRAb）相关的弥漫性甲状腺肿。尽管甲状腺肿形成的原因被认为是TRAb，但人类成年甲状腺细胞在体外有限的生长模式使得这一结论是基于对非人类甲状腺细胞生长的研究得出的。我们最近描述了一种使用胎儿甲状腺细胞测量人类甲状腺细胞增殖和功能的可预测且精确的技术，并利用该系统研究TRAb对人类甲状腺细胞生长的影响。来自正常个体（n = 5）的高度纯化的人免疫球蛋白G（hIgG）制剂对人类甲状腺细胞生长没有显著影响。然而，来自可检测到TRAb的患者的hIgG（TRAb-hIgG）（n = 13）在4天内诱导细胞外cAMP呈剂量相关增加（在0.1 mg/ml时达到最大效应），并使人类甲状腺细胞生长增加3倍（在1.5 mg/ml时达到最大效应）。在基础甲状腺细胞培养条件下，可检测到原癌基因c-fos特异性的mRNA水平，但较低，添加TRAb-hIgG可显著且迅速地诱导其表达，而正常hIgG则不能。这些数据表明在同源人类甲状腺细胞培养系统中TRAb-hIgG可诱导细胞生长。这些观察结果支持这样的假设，即格雷夫斯病患者甲状腺肿的形成至少部分是由于TRAb-hIgG的生长刺激活性所致。
