Hirooka Y, Mitsuma T, Nogimori T, Ishizuki Y, Sakai J, Naruse M, Fukayama M
Fourth Department of Internal Medicine, Aichi Medical University, Japan.
Life Sci. 1993;53(8):659-64. doi: 10.1016/0024-3205(93)90276-9.
The present study was designed to examine whether thyroid stimulating antibodies (TSAb) against the mutated or non-mutated peptide of human TSH receptor stimulates release of thyroid hormones in mice in vivo. We generated antibodies against mutated TSH receptor peptide TSH-R-HIS17 and non-mutated TSH receptor peptide TSH-R-ASP17 immunizing the peptides to rabbits. We isolated immunoglobulin G (IgG) from these antibodies and injected iv into male ddy mice. Control mice were injected iv with bTSH or TSAb-negative normal rabbit IgG. Serum T3 and T4 concentrations were elevated after the administration of bTSH in a dose-dependent manner. Serum T3 and T4 concentrations were significantly elevated after the injection of IgG from the rabbit antibodies with TSAb activity produced against TSH-R-HIS17. However serum T3 and T4 remained within normal levels after the injection of IgG from the rabbit antibodies without TSAb activity toward TSH-R-ASP17. The present data offer in vivo support of the IgG with TSAb activity interaction with the TSH receptor of the thyroid and raise the possibility that TSAb against mutated human TSH receptor peptide might be contributed to induce thyroid hyperfunction.
本研究旨在检测针对人促甲状腺激素（TSH）受体突变或非突变肽段的促甲状腺素抗体（TSAb）是否能在体内刺激小鼠甲状腺激素的释放。我们通过将突变的TSH受体肽段TSH-R-HIS17和非突变的TSH受体肽段TSH-R-ASP17免疫兔子，制备了相应抗体。我们从这些抗体中分离出免疫球蛋白G（IgG），并静脉注射到雄性ddy小鼠体内。对照小鼠静脉注射牛TSH（bTSH）或TSAb阴性的正常兔IgG。给予bTSH后，血清三碘甲状腺原氨酸（T3）和甲状腺素（T4）浓度呈剂量依赖性升高。注射针对TSH-R-HIS17产生的具有TSAb活性的兔抗体IgG后，血清T3和T4浓度显著升高。然而，注射对TSH-R-ASP17无TSAb活性的兔抗体IgG后，血清T3和T4仍维持在正常水平。本研究数据为具有TSAb活性的IgG与甲状腺TSH受体的相互作用提供了体内证据，并提示针对突变型人TSH受体肽段的TSAb可能参与诱导甲状腺功能亢进。
