Constant R B, Weintraub B D
Endocrinology. 1986 Dec;119(6):2720-7. doi: 10.1210/endo-119-6-2720.
We compared the MCR, volume of distribution, and rapid phase (rt1/2) and slow phase half-lives of purified pituitary rat (r) TSH, TSH from crude pituitary extracts of normal and hypothyroid rats, TSH from hypothyroid rat sera, and TSH secreted from hypothyroid rat pituitaries incubated in vitro. For 3 h after iv bolus injection into euthyroid rats, 125I-labeled rTSH was determined by acid precipitation in serum and various organs, and unlabeled TSH was measured by RIA. The MCR of TSH from normal pituitary extracts (0.53 +/- 0.02 ml/min) was similar to that of unlabeled purified rTSH (0.52 +/- 0.03), while those from hypothyroid pituitary extracts (0.32 +/- 0.03) and hypothyroid sera (0.33 +/- 0.01) were decreased. The reduced MCR of TSH from hypothyroid pituitaries was due to a decreased distribution volume (8.4 +/- 0.6 ml) compared to that from normal pituitaries (11.4 +/- 0.7) and hypothyroid sera (10.9 +/- 0.8). The decreased MCR of circulating TSH from hypothyroid sera reflected an increase in its rt1/2 (12.6 +/- 0.5 min) vs. that from both normal (5.1 +/- 0.5) and hypothyroid (5.7 +/- 0.4) pituitaries. The rt1/2 of secreted TSH from incubated hypothyroid rat pituitaries (8.5 +/- 0.9) was intermediate between those of circulating and pituitary forms of hypothyroid rTSH. The clearances of intact bovine TSH (bTSH) and deglycosylated bTSH (dg-bTSH) were compared. The dg-bTSH MCR was found to be increased (0.71 +/- 0.02 ml/min) compared to that of bTSH (0.59 +/- 0.02), primarily due to a decreased rt1/2 for dg-bTSH (3.8 +/- 0.1 min) vs. bTSH (4.7 +/- 0.2). Uptake of purified [125I]rTSH was highest in the kidney at all times, varying from 43% of the injected dose at 5 min to 54% at 180 min. We conclude that in the euthyroid rat, 1) the metabolic clearance of TSH differs between pituitary and serum forms and appears to depend on specific molecular features that vary with the physiological state of the animal from which the TSH is derived; 2) since chemical deglycosylation increased the clearance of TSH, we speculate that the chemical basis for changes in TSH clearance may be related to alterations in its carbohydrate structure; and 3) for normal pituitary TSH, the kidney is the major organ of clearance.
我们比较了纯化的大鼠垂体促甲状腺激素（rTSH）、正常和甲状腺功能减退大鼠垂体粗提物中的促甲状腺激素、甲状腺功能减退大鼠血清中的促甲状腺激素以及体外培养的甲状腺功能减退大鼠垂体分泌的促甲状腺激素的代谢清除率（MCR）、分布容积、快速相半衰期（rt1/2）和缓慢相半衰期。将125I标记的rTSH静脉推注到甲状腺功能正常的大鼠体内3小时后，通过血清和各器官中的酸沉淀法测定其含量，并用放射免疫分析法（RIA）测定未标记的促甲状腺激素。正常垂体提取物中促甲状腺激素的MCR（0.53±0.02ml/min）与未标记的纯化rTSH（0.52±0.03）相似，而甲状腺功能减退垂体提取物（0.32±0.03）和甲状腺功能减退血清（0.33±0.01）中的MCR则降低。甲状腺功能减退垂体中促甲状腺激素MCR降低是由于分布容积减小（8.4±0.6ml），而正常垂体（11.4±0.7）和甲状腺功能减退血清（10.9±0.8）中的分布容积较大。甲状腺功能减退血清中循环促甲状腺激素MCR降低反映其rt1/2增加（12.6±0.5分钟），而正常（5.1±0.5）和甲状腺功能减退（5.7±0.4）垂体中的rt1/2较短。体外培养的甲状腺功能减退大鼠垂体分泌的促甲状腺激素的rt1/2（8.5±0.9）介于甲状腺功能减退rTSH的循环形式和垂体形式之间。比较了完整牛促甲状腺激素（bTSH）和去糖基化牛促甲状腺激素（dg-bTSH）的清除率。发现dg-bTSH的MCR（0.71±0.02ml/min）高于bTSH（0.59±0.02），主要是因为dg-bTSH的rt1/2（3.8±0.1分钟）比bTSH（4.7±0.2分钟）短。纯化的[125I]rTSH在肾脏中的摄取在所有时间都是最高的，从注射后5分钟时占注射剂量的43%到180分钟时占54%。我们得出结论，在甲状腺功能正常的大鼠中，1）垂体形式和血清形式的促甲状腺激素的代谢清除率不同，似乎取决于特定的分子特征，这些特征随促甲状腺激素来源动物的生理状态而变化；2）由于化学去糖基化增加了促甲状腺激素的清除率，我们推测促甲状腺激素清除率变化的化学基础可能与其碳水化合物结构的改变有关；3）对于正常垂体促甲状腺激素，肾脏是主要的清除器官。
