Shoda Y, Kondo Y, Kobayashi I
First Department of Internal Medicine, Gunma University, Maebashi, Japan.
J Clin Endocrinol Metab. 1993 Jul;77(1):94-7. doi: 10.1210/jcem.77.1.8100833.
TSH induced I- efflux in FRTL-5 cells, a cell line derived from normal rat thyroid cells, is not mediated by cAMP but intracellular Ca2+ signaling. Graves' patient immunoglobulin G is known to activate the thyroidal cAMP pathway, but little is known about the activation of Ca2+ signaling. We report here that, similarly to TSH, the polyethylenglycol-precipitated serum fraction of Graves' patients induces I- efflux in FRTL-5 cells. The cells grown in the presence of TSH were incubated for 3 weeks in a Ham's 10 medium containing 1% CS, insulin, and hydrocortison for TSH depletion. After preincubating with 125I-iodide for 50 min to label intracellular iodide, the cells were challenged by serum samples for 1 min. The addition of normal pooled-serum hardly affected the I- efflux. The Graves' immunoglobulin G fractions dose-dependently stimulated I- efflux. The averaged potency of 12 patients' sera relative to the values of the pooled serum as 100% was 217 +/- 56.4%. This value was significantly higher (P < 0.001) than that for eight normal subjects (110 +/- 16.1%). The present study is the demonstration suggesting that Graves' thyrotoxicosis is mediated not only by an adenylate cyclase-cAMP system but also by a phospholipid-Ca2+ system.
促甲状腺激素（TSH）可诱导源自正常大鼠甲状腺细胞的FRTL-5细胞发生碘外流，这一过程不是由环磷酸腺苷（cAMP）介导的，而是由细胞内钙离子信号传导介导的。已知格雷夫斯病（Graves' disease）患者的免疫球蛋白G可激活甲状腺的cAMP信号通路，但对于钙离子信号传导的激活情况却知之甚少。我们在此报告，与TSH类似，格雷夫斯病患者经聚乙二醇沉淀的血清组分可诱导FRTL-5细胞发生碘外流。将在TSH存在下生长的细胞在含有1%小牛血清、胰岛素和氢化可的松的哈姆氏10培养基中孵育3周以耗尽TSH。在用125I-碘化物预孵育50分钟以标记细胞内碘后，用血清样本刺激细胞1分钟。添加正常混合血清对碘外流几乎没有影响。格雷夫斯病免疫球蛋白G组分可剂量依赖性地刺激碘外流。12例患者血清相对于混合血清值（设为100%）的平均效力为217±56.4%。该值显著高于8名正常受试者的（110±16.1%）（P<0.001）。本研究表明，格雷夫斯病甲状腺毒症不仅由腺苷酸环化酶-cAMP系统介导，还由磷脂-钙离子系统介导。
