Studies on the mode of action of TSBAb

TSBAb作用方式的研究

• 批准号: 05807086
• 负责人: OCHI Yukio
• 金额: $ 1.22万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05807086/
• 关键词: TSH receptor; TSH receptor antibody; TSH stimulation blocking antibody; Thyroid membrane; guinea-pig epididymal fat membrane; モルモット脂肪膜; ProteinL

The thyroid stimulation blocking antibody (TSBAb) which block the stimulatory effect of TSH on thyroid has been suggested as the causal factor of hypothyroidism.There are two types of TSBAb, one type has a blocking action on TSH by its direct binding to the TSH receptor [TSH binding inhibitory immunoblobulin (TBII) positive blocking antibody] and the other type has a blocking action without affecting TSH binding to its receptor (TBII negative blocking antibody). The study on mode of action of TSBAb was performed.1. The action of TSBAb on thyroid cell membraneThe TSBAb with high TBII activities significantly blocked TSH-stimulated cAMP production in porcine thyroid cells (PTC). However, there was no blocking action of TSBAb on the cAMP increase stimulated by forskolin, GTP gamma S,or NaF in isolated porcine thyroid membrane (PTM). The TSBAb activity was absorbed with PTM,but was not absorbed with guinea-pig epididymal fat membrane in some cases in spite of the absorption of the TBII activity in TSBAb-IgG by these two membranes. This suggests that TSBAb may block TSH action either via the TSH receptor or via a non-TSH receptor component of the thyroid membrane and not at a post receptor level.2. Production of TSBAb in experimental rabbitsThe produced antibody in rabbits against PTM showed the TSBAb activity in spite of negative TBII activity. The fact suggests that this type of TSBAb may be produced against any antigen of thyroid membrane origin except the TSH receptor.3.Appearence of thyroid stimulating activity from TSBAb-IgG by protease digestionThe innocent action (without thyroid stimulating activity) of TSBAb-IgG was converted to the thyroid stimulating activity by protease digestion. The thyroid stimulating activity located in Fab and the much smaller component fraction.

甲状腺刺激阻断抗体（TSBAb）阻断TSH对甲状腺的刺激作用，被认为是甲状腺功能减退症的病因，TSBAb有两种类型，一种类型通过其与TSH受体的直接结合对TSH具有阻断作用[TSH结合抑制性免疫球蛋白（TBII）阳性阻断抗体]，另一种类型具有阻断作用而不影响TSH与其受体的结合（TBII阴性封闭抗体）。对TSBAb的作用机制进行了研究. TSBAb对甲状腺细胞膜的作用高TBII活性的TSBAb能显著抑制TSH刺激的猪甲状腺细胞（PTC）cAMP的产生。然而，有没有阻断作用TSBAb对cAMP的增加刺激forskolin，GTP γ S，或NaF在离体猪甲状腺膜（PTM）。TSBAb-IgG中的TBII活性可被PTM吸收，但在某些情况下不被豚鼠附睾脂肪膜吸收。这表明TSBAb可能通过TSH受体或甲状腺膜的非TSH受体成分而不是在受体后水平阻断TSH作用。实验兔TSBAb的产生尽管TBII活性为阴性，但所产生的兔抗PTM抗体仍显示TSBAb活性。这一事实表明，这种类型的TSBAb可以针对除TSH受体以外的任何甲状腺膜来源的抗原产生。3.蛋白酶消化TSBAb-IgG的甲状腺刺激活性的出现TSBAb-IgG的无害作用（无甲状腺刺激活性）通过蛋白酶消化转化为甲状腺刺激活性。促甲状腺激素活性主要位于Fab段和较小的组分中。

项目成果

Ochi Yukio, et al.: "Anti-thyroical autoantibody" Medical Practice. 11- (8) (in Japanese). 1393-1398 (1994)

Ochi Yukio 等人：“抗甲状腺自身抗体”医疗实践。

越智 幸男: "臨床検査ガイド'95" 文光堂(東京), 1044 (1995)

Yukio Ochi：“临床测试指南 95”Bunkodo（东京），1044（1995）

Inui Takehiro, et al.: "Production of thyroid stimulation blocking antibody without TSH receptor binding activity in rabbits with experimental autoimmune thyroditis" Hormone and Metabolic Research. 26- (1). 5-8 (1994)

Inui Takehiro 等人：“在患有实验性自身免疫性甲状腺炎的兔子中生产不具有 TSH 受体结合活性的甲状腺刺激阻断抗体”激素和代谢研究。

Chen Wen: "Studies on the action of thyroid stimulation blocking antibody(TSBAb)on thyroid thyroid cell membrane" Thyroid. 4. 479-483 (1994)

陈文：“甲状腺刺激阻断抗体（TSBAb）对甲状腺细胞膜作用的研究” 甲状腺。

Chen Wen, et al.: "Stimulatory action of pituitary adenylate cyclase-activating polypeptide (PACAP) on thyroid gland" Biochemical and Biophysical Research communications. 194- (2). 923-929 (1993)

陈文等：“垂体腺苷酸环化酶激活多肽（PACAP）对甲状腺的刺激作用”生物化学与生物物理研究通讯。