Bidey S P, Ekins R P
Clin Endocrinol (Oxf). 1986 Apr;24(4):447-58. doi: 10.1111/j.1365-2265.1986.tb01650.x.
The rat thyroid cell strain FRTL-5 was used to investigate the relationship between cyclic AMP and iodide accumulation responses to thyroid-stimulating immunoglobulins (TSIg). Immunoglobulin G-enriched precipitates of sera from 19 of 21 (90%) newly-diagnosed Graves' disease patients gave significant (P less than 0.01) accumulation of iodide (125I), and 16 of these also stimulated intracellular cyclic AMP. Correlation was poor however, with certain TSIg preparations giving widely divergent responses. After initiation of antithyroid treatment, 40% of sera investigated contained TSIg detectable in both bioassay systems, and all but one of the remainder were stimulatory in one of the two bioassays. All patients in remission were devoid of detectable TSIg as determined by iodide accumulation, although a single preparation stimulated cyclic AMP accumulation. LATS-B, a lyophilized reference serum preparation containing high TSIg activity, enhanced iodide accumulation, which showed evidence of correlation with intracellular cyclic AMP at doses above 0.5 mU/ml. At lower doses, iodide accumulation was observed in the absence of detectable cyclic AMP accumulation. TSH and LATS-B-induced iodide accumulation were enhanced, and iodide efflux reduced, by the anion channel blocker 4-4' diisothiocyanate stilbene 2,2' disulphonic acid (DIDS). In contrast, Ig-enriched fractions of normal sera decreased both basal and stimulated iodide accumulation, but were without effect on efflux. TSIg from untreated Graves' sera gave widely-differing iodide accumulation responses which showed poor correlation with both intracellular cyclic AMP and cyclic-AMP-independent iodide efflux. This clear dissociation of responses to serum Ig preparations suggests that iodide uptake in FRTL-5 cells, which do not organify iodide, may be subject to variable effects of non-TSIg components of Graves' sera, on both iodide uptake itself, and as inhibitors of TSIg-induced accumulation of intracellular cyclic AMP.
采用大鼠甲状腺细胞系FRTL-5研究环磷酸腺苷（cAMP）与甲状腺刺激免疫球蛋白（TSIg）刺激下碘摄取反应之间的关系。21例新诊断的格雷夫斯病患者中，19例（90%）血清的免疫球蛋白G富集沉淀物使碘（125I）摄取显著增加（P<0.01），其中16例还刺激了细胞内cAMP的生成。然而，相关性较差，某些TSIg制剂的反应差异很大。开始抗甲状腺治疗后，40%的受检血清在两种生物测定系统中均可检测到TSIg，其余血清除1例外在两种生物测定中的一种有刺激作用。所有缓解期患者经碘摄取测定均未检测到可检测的TSIg，尽管有一种制剂刺激了cAMP的生成。LATS-B是一种含有高TSIg活性的冻干参考血清制剂，可增强碘摄取，在剂量高于0.5 mU/ml时显示出与细胞内cAMP相关的证据。在较低剂量时，在未检测到cAMP生成的情况下观察到碘摄取。阴离子通道阻滞剂4,4'-二异硫氰酸芪-2,2'-二磺酸（DIDS）可增强促甲状腺激素（TSH）和LATS-B诱导的碘摄取，并减少碘外流。相比之下，正常血清的免疫球蛋白富集部分可降低基础碘摄取和刺激后的碘摄取，但对碘外流无影响。未经治疗的格雷夫斯病血清中的TSIg引起的碘摄取反应差异很大，与细胞内cAMP和不依赖cAMP的碘外流均相关性较差。对血清免疫球蛋白制剂反应的这种明显分离表明，在不进行碘有机化的FRTL-5细胞中，碘摄取可能受到格雷夫斯病血清中非TSIg成分对碘摄取本身以及作为TSIg诱导的细胞内cAMP生成抑制剂的多种影响。
