Hoermann R, Schumm-Draeger P M, Mann K
Medical Department II, Klinikum Grosshadern, University of Munich, Germany.
Thyroid. 1993 Winter;3(4):273-8. doi: 10.1089/thy.1993.3.273.
Thyrotropin (TSH) receptor is the main autoantigen and the target of thyroid-stimulating antibodies in Graves' disease. In the present studies, in order to shed further light on the role of TSH receptor in thyroid autoimmune disease, we investigated the effects of TSH receptor blockade on functional and immunological responses to thyroid stimulation by Graves' immunoglobulins in the nude mouse bearing human thyroid transplants. Injecting the nude mice with purified Graves' immunoglobulins G resulted in a dose-dependent stimulation of thyroid hormone production, an inducement of cellular hypertrophy of transplant thyrocytes, and an expression of the HLA-DR antigen by up to 75% of the transplant thyroid follicular cells. Treatment of the animals with the TSH receptor antagonist asialoagalacto-hCG was able to inhibit the stimulation by Graves' immunoglobulins G of thyroxine production, cellular hypertrophy of transplant thyrocytes, and HLA-DR expression by thyroid follicular cells in the human transplants. The present data provide direct evidence for an involvement of the human TSH receptor in mediating both the functional disturbance (hyperthyroidism) and the immunological disorder in Graves' disease and add further support to the concept of using TSH receptor antagonists in the management of the disease.
促甲状腺激素（TSH）受体是格雷夫斯病中的主要自身抗原及促甲状腺抗体的靶点。在本研究中，为了进一步阐明TSH受体在甲状腺自身免疫性疾病中的作用，我们在移植了人甲状腺的裸鼠中，研究了TSH受体阻断对格雷夫斯病免疫球蛋白刺激甲状腺所产生的功能及免疫反应的影响。给裸鼠注射纯化的格雷夫斯病免疫球蛋白G可导致甲状腺激素产生呈剂量依赖性增加、移植甲状腺细胞出现细胞肥大，且高达75%的移植甲状腺滤泡细胞表达HLA-DR抗原。用TSH受体拮抗剂去唾液酸半乳糖基化人绒毛膜促性腺激素（asialoagalacto-hCG）处理动物，能够抑制格雷夫斯病免疫球蛋白G对甲状腺素产生的刺激、移植甲状腺细胞的细胞肥大以及人移植甲状腺滤泡细胞的HLA-DR表达。目前的数据为人类TSH受体参与介导格雷夫斯病的功能紊乱（甲状腺功能亢进）和免疫紊乱提供了直接证据，并进一步支持了使用TSH受体拮抗剂治疗该疾病的理念。
