Abe Y
Nihon Naibunpi Gakkai Zasshi. 1980 May;56(5):739-53. doi: 10.1507/endocrine1927.56.5_739.
Most current etiologic concepts of Graves' disease postulate that this is an autoimmune disorder. A humoral factor, such as thyroid stimulating immunoglobulin, may be the mediator. On the other hand, it has also been suggested that abnormalities in the thyroid gland itself might be responsible for hyperfunction of the gland in Graves' disease. The true etiology of Graves' disease is still unknown. Similarly, the pathogenesis of the ophthalmic changes of Graves' disease is obscure, but immune mechanisms figure prominently in current hypotheses of the pathogenesis. It has been suggested that human adipose cell membranes have TSH receptors and that antibodies reacting with the receptors may stimulate fat cells. In this study, we have evaluated TSH receptor and adenylate cyclase of Graves' thyroid glands. Furthermore, we have investigated those of retro-orbital and the other adipose tissues in the guinea pig and in man. Human thyroid tissues were obtained at surgery and immediately minced homogenized with a loose-fitting Dounce homogenizer. A part of 10,000 g pellet of the homogenate was used for adenylate cyclase assay. The rest of the pellet was further purified by a discontinuous sucrose gradient ultracentrifugation, and the plasma membrane fraction was used for the receptor assay. The 125I-TSH binding to the fraction was measured, and the affinity constant (Ka) and capacity (Ro) were obtained from Scatchard plots using Rosenthal's method of analysis. Normal thyroid tissue contained high affinity (Ka = 2.4 x 10(10) M-1; Ro = 0.9 pmole/mg protein) and low affinity (Ka = 1.9 x 10(8) M-1; Ro = 386 pmole/mg protein) receptors. The two orders of TSH receptor were also found in Graves' thyroid tissue. The affinity constant and capacity of high affinity receptors were identical with those of normal thyroids, but the affinity constant of low affinity receptors was lower in Graves' thyroid (P less than 0.05). The basal adenylate cyclase activity in normal thyroid tissues was 0.35 nmole/10 min/mg protein. The activity rose to 280% of basal with 166 mU/ml of TSH and 680% of basal with 10 mM of NaF. These values obtained in Graves' disease were not significantly different from the values of normal thyroids. It is concluded that thyroid hyperfunction in Graves' disease is probably not the result of an intrinsic abnormality of the TSH receptor-adenylate cyclase system. Human retro-orbital adipose tissue was obtained at surgery from patients of Graves' exophthalmos or malignant neoplasm of accessory sinus. Guinea pigs tissue was obtained from 250g male animals. We were unable to demonstrate high affinity TSH receptor in human retro-orbital fat, perirenal fat or guinea pig retro-orbital fat. In contrast, guinea pig epididymal fat membranes showed TSH receptor characteristics similar to guinea pig thyroid membranes. In human adipose tissue, TSH did not stimulate the adenylate cyclase activity, although NaF definitely stimulated the enzyme...
目前，大多数关于格雷夫斯病的病因学概念假定这是一种自身免疫性疾病。一种体液因子，如促甲状腺免疫球蛋白，可能是介导物。另一方面，也有人提出甲状腺自身的异常可能是格雷夫斯病中甲状腺功能亢进的原因。格雷夫斯病的真正病因仍然未知。同样，格雷夫斯病眼部病变的发病机制也不清楚，但免疫机制在当前发病机制假说中占据重要地位。有人提出人类脂肪细胞膜有促甲状腺激素（TSH）受体，与这些受体反应的抗体可能刺激脂肪细胞。在本研究中，我们评估了格雷夫斯病甲状腺的TSH受体和腺苷酸环化酶。此外，我们还研究了豚鼠和人类眼眶后及其他脂肪组织中的TSH受体和腺苷酸环化酶。人类甲状腺组织在手术时获取，立即用松配合的杜恩斯匀浆器切碎匀浆。匀浆物10000g沉淀的一部分用于腺苷酸环化酶测定。沉淀的其余部分通过不连续蔗糖梯度超速离心进一步纯化，质膜部分用于受体测定。测量125I-TSH与该部分的结合，并使用罗森塔尔分析方法从斯卡查德图获得亲和常数（Ka）和容量（Ro）。正常甲状腺组织含有高亲和力（Ka = 2.4×10¹⁰ M⁻¹；Ro = 0.9皮摩尔/毫克蛋白）和低亲和力（Ka = 1.9×10⁸ M⁻¹；Ro = 386皮摩尔/毫克蛋白）受体。在格雷夫斯病甲状腺组织中也发现了这两种TSH受体类型。高亲和力受体的亲和常数和容量与正常甲状腺相同，但格雷夫斯病甲状腺中低亲和力受体的亲和常数较低（P＜0.05）。正常甲状腺组织中的基础腺苷酸环化酶活性为0.35纳摩尔/10分钟/毫克蛋白。用166毫单位/毫升的TSH时活性升至基础值的280%，用10毫摩尔的氟化钠时活性升至基础值的680%。在格雷夫斯病中获得的这些值与正常甲状腺的值无显著差异。结论是，格雷夫斯病中的甲状腺功能亢进可能不是TSH受体-腺苷酸环化酶系统内在异常的结果。人类眼眶后脂肪组织在手术时从格雷夫斯病突眼患者或副鼻窦恶性肿瘤患者获取。豚鼠组织从250克雄性动物获取。我们未能在人类眼眶后脂肪、肾周脂肪或豚鼠眼眶后脂肪中证明高亲和力TSH受体。相比之下，豚鼠附睾脂肪膜显示出与豚鼠甲状腺膜相似的TSH受体特征。在人类脂肪组织中，TSH不刺激腺苷酸环化酶活性，尽管氟化钠肯定能刺激该酶……
