Clark O H, Gerend P L, Nissenson R A
J Clin Endocrinol Metab. 1982 Jun;54(6):1157-63. doi: 10.1210/jcem-54-6-1157.
The effects of bovine TSH (bTSH) and bovine (bTg) and human thyroglobulin (hTg) on the binding of [125I] bTSH and the activation of adenylate cyclase (AC) were studied in both normal and neoplastic human thyroid homogenates in vitro using adenylate cyclase conditions. [125I]bTSH bound specifically and with high affinity to a particulate fraction from normal thyroid and from benign and malignant thyroid neoplasms; this binding was inhibited by unlabeled bTSH (approximate Kd = 10.0 mU/ml for normal tissue; Kd = 2.5 mU/ml for thyroid neoplasms). Half-maximal activation of AC was obtained at a TSH concentration of approximately 2.5 mU/ml for both normal and neoplastic thyroid tissue, indicating that the high affinity TSH receptors are coupled to AC, at least in the neoplastic thyroid tissue. bTg and hTg did not inhibit [125I]bTSH binding to high affinity TSH receptors in either normal or neoplastic thyroid tissue. bTSH increased AC activity up to 25-fold in neoplastic thyroid tissue and up to 4-fold in normal thyroid tissue, whereas at concentrations up to 1 mg/ml, bTg had no effect. The current study demonstrates that bTSH binds to specific, high affinity receptors and stimulates AC activity in both normal and neoplastic thyroid tissue. bTg and hTg, under the conditions used in this experiment, do not influence TSH binding to its high affinity receptor in these tissues. Since Tg does not influence high affinity TSH binding or AC activity in a particulate fraction rich in plasma membranes from normal or neoplastic thyroid tissue, it is unlikely to have a modulating role on TSH action at the thyroid plasma membrane.
利用腺苷酸环化酶条件，在体外对正常和肿瘤性人甲状腺匀浆中牛促甲状腺激素（bTSH）、牛甲状腺球蛋白（bTg）和人甲状腺球蛋白（hTg）对[125I]bTSH结合及腺苷酸环化酶（AC）激活的影响进行了研究。[125I]bTSH特异性且高亲和力地结合于正常甲状腺以及良性和恶性甲状腺肿瘤的微粒体部分；未标记的bTSH可抑制这种结合（正常组织的近似解离常数Kd = 10.0 mU/ml；甲状腺肿瘤的Kd = 2.5 mU/ml）。正常和肿瘤性甲状腺组织在促甲状腺激素浓度约为2.5 mU/ml时均可获得AC的半数最大激活，这表明高亲和力促甲状腺激素受体与AC偶联，至少在肿瘤性甲状腺组织中如此。bTg和hTg在正常或肿瘤性甲状腺组织中均不抑制[125I]bTSH与高亲和力促甲状腺激素受体的结合。bTSH可使肿瘤性甲状腺组织中的AC活性增加高达25倍，并使正常甲状腺组织中的AC活性增加高达4倍，而在浓度高达1 mg/ml时，bTg无作用。当前研究表明，bTSH在正常和肿瘤性甲状腺组织中均能结合特异性高亲和力受体并刺激AC活性。在本实验所用条件下，bTg和hTg不影响促甲状腺激素与其在这些组织中的高亲和力受体的结合。由于甲状腺球蛋白在富含正常或肿瘤性甲状腺组织质膜的微粒体部分中不影响高亲和力促甲状腺激素结合或AC活性，因此它不太可能对甲状腺质膜上促甲状腺激素的作用具有调节作用。
