Silva J E, Larsen P R
Endocrinology. 1978 Jun;102(6):1783-96. doi: 10.1210/endo-102-6-1783.
The peripheral metabolism and metabolic clearance rate (MCR) of homologous TSH was studied in euthyroid and hypothyroid rats. Incubation of freshly labeled [125I]iodo-TSH with rat serum revealed a labeled nonimmunoreactive protein in the void volume of a Sephadex G-100 column which could not be detected by conventional chromatographic purification. Removal of this contaminant from the tracer reduced the nonspecific binding in the absence of serum and increased the binding of tracer in the absence of added exogenous TSH. Injection of [125I]iodo-TSH into rats was followed within 15 min by the appearance of at least three labeled protein components. Gel filtration showed that these peaks were trichloroacetic acid (TCA)-precipitable proteins of larger molecular weight than TSH, but not all were precipitable by antibody to rat TSH. The disappearance rate of TCA-precipitable 125I (t1/2 = 28 min) was significantly longer than the disappearance rate of immunoprecipitable 125I (t1/2 = 22 min). The disappearance rate of immunoprecipitable [125I]iodo-TSH was identical to that of injected purified rat TSH and of the TRH-induced TSH increment in euthyroid rats. The disappearance rate os suppressible TSH (after 100 microgram T3) in hypothyroid animals was only slightly longer than the rate of disappearance of immunoprecipitable [125I]iodo-TSH (40 vs. 36 min) in the same rats. The calculated MCR of TSH was slightly lower (P less than 0.05) in hypothyroid rats (18.3 +/- 3.0 ml/h/100 g BW, mean +/- SD) than it was in euthyroid rats (22.6 +/- 2.1). The pituitary TSH concentration in hypothyroid rats was 29 mU/mg wet wt, similar to that of euthyroid animals. These results indicate that the turnover rate of pituitary TSH in hypothyroid rats with serum TSH concentrations of 1400-3000 microunit/ml is 7-14 times/day. Therefore, the significant increase we observed in pituitary TSH concentration 1 h after T4 (1.5 microgram/100 g BW) or T3 (0.15 microgram/100 g BW) administration indicates that the 35% decrease in plasma TSH at this interval is due to inhibition of TSH release, not to inhibition of TSH synthesis.
在甲状腺功能正常和甲状腺功能减退的大鼠中研究了同源促甲状腺激素（TSH）的外周代谢及代谢清除率（MCR）。将新标记的[125I]碘 - TSH与大鼠血清一起孵育，发现在Sephadex G - 100柱的空体积中有一种标记的非免疫反应性蛋白，常规色谱纯化无法检测到该蛋白。从示踪剂中去除这种污染物可降低无血清时的非特异性结合，并增加无添加外源性TSH时示踪剂的结合。给大鼠注射[125I]碘 - TSH后15分钟内，至少出现三种标记的蛋白质成分。凝胶过滤显示，这些峰是分子量比TSH大的三氯乙酸（TCA）可沉淀蛋白，但并非所有蛋白都能被抗大鼠TSH抗体沉淀。TCA可沉淀的125I的消失率（t1/2 = 28分钟）明显长于免疫沉淀的125I的消失率（t1/2 = 22分钟）。免疫沉淀的[125I]碘 - TSH的消失率与注射的纯化大鼠TSH以及甲状腺功能正常大鼠中促甲状腺激素释放激素（TRH）诱导的TSH增加的消失率相同。甲状腺功能减退动物中可被抑制的TSH（100微克T3后）的消失率仅比同一只大鼠中免疫沉淀的[125I]碘 - TSH的消失率略长（40分钟对36分钟）。计算得出，甲状腺功能减退大鼠中TSH的MCR（18.3±3.0 ml/h/100 g体重，平均值±标准差）略低于甲状腺功能正常大鼠（22.6±2.1）（P＜0.05）。甲状腺功能减退大鼠垂体中的TSH浓度为29 mU/mg湿重，与甲状腺功能正常的动物相似。这些结果表明，血清TSH浓度为1400 - 3000微单位/毫升的甲状腺功能减退大鼠垂体TSH的周转率为每天7 - 14次。因此，我们观察到在给予T4（1.5微克/100 g体重）或T3（0.15微克/100 g体重）1小时后垂体TSH浓度显著升高，这表明在此时间段血浆TSH降低35%是由于TSH释放受到抑制，而非TSH合成受到抑制。
