Inhibition of thyroid-stimulating hormone stimulation of protein kinase, glucose oxidation, and phospholipid synthesis in thyroid slices previously exposed to the hormone.
Inhibition of thyroid-stimulating hormone stimulation of protein kinase, glucose oxidation, and phospholipid synthesis in thyroid slices previously exposed to the hormone.
复制标题
抑制促甲状腺激素对先前暴露于激素的甲状腺切片中的蛋白激酶、葡萄糖氧化和磷脂合成的刺激。
DOI：
10.1172/jci108684
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发表时间：
1977
期刊：
影响因子：
--
通讯作者：
M. Kerins
中科院分区：
文献类型：
--
作者：
J. Field;G. Bloom;C. Chou;M. Kerins
先前将甲状腺切片暴露于促甲状腺素 (TSH) 会导致随后对该激素对环 AMP 系统的刺激产生耐药性。尽管抑制不完全，但我们检查了环 AMP 的减少是否足以改变 TSH 的其他代谢作用。将牛或狗甲状腺切片与或不与5-100 mU/ml TSH一起孵育1-2小时，洗涤，然后在不加激素的情况下孵育1-2小时。然后将最初未暴露于 TSH 的一半切片与缓冲液一起孵育，另一半暴露于 5-100 mU/ml TSH。最初与 TSH 一起孵育的切片在第三次孵育中也可与或不与 TSH 一起孵育。在不应期，尽管激素仍引起环磷酸腺苷浓度有所增加，但蛋白激酶的 TSH 激活受到抑制。然而，当切片在第三次孵育期间与二丁酰环 AMP 一起孵育时，蛋白激酶活性对二丁酰环 AMP 完全敏感。在先前与激素一起孵育的甲状腺切片中，TSH 对葡萄糖氧化的刺激显着减少。在不应期，前列腺素E1和二丁酰环AMP引起的葡萄糖氧化刺激也显着减弱，但乙酰胆碱引起的葡萄糖氧化刺激却没有明显减弱。因此，尽管二丁酰环AMP可以在不应期期间完全激活蛋白激酶活性，但其对葡萄糖氧化的作用仍然受到抑制，这表明导致这种不应期的代谢阻断远离蛋白激酶的激活。在不应期期间，TSH 和乙酰胆碱对 32Pi 掺入磷脂的刺激也受到抑制。尽管 TSH 的刺激作用降低，但甲状腺切片与 TSH 的预先孵育并未改变 125ITSH 的结合。这些结果表明，TSH 受体的变化并不是不应性的发生的原因，除了腺苷酸环化酶的激活之外，其他代谢位点似乎也参与其中。
Prior exposure of thyroid slices to thyrotropin (TSH) induced refractoriness to subsequent stimulation of the cyclic AMP system by the hormone. Although the inhibition is incomplete, we examined whether the reduction in cyclic AMP was sufficient to alter other metabolic effects of TSH. Bovine or dog thyroid slices were incubated with or without 5-100 mU/ml TSH for 1-2h, washed, and then incubated without hormone for 1-2h. Half of the slices not exposed to TSH initially were then incubated with buffer and half were exposed to 5-100 mU/ml TSH. Slices initially incubated with TSH were also incubated with or without TSH in the third incubation. During the refractory period, TSH activation of protein kinase was inhibited even though the hormone still caused some increase in cyclic AMP concentrations. However, protein kinase activity was fully responsive to dibutyryl cyclic AMP when slices were incubated with it during the third incubation. Stimulation of glucose oxidation by TSH was significantly decreased in thyroid slices previously incubated with the hormone. During refractoriness, stimulation of glucose oxidation caused by prostaglandin E1 and dibutyryl cyclic AMP was also significantly diminished but that due to acetylcholine was not. Thus even though dibutyryl cyclic AMP could fully activate protein kinase activity during refractoriness, its effect on glucose oxidation was still inhibited, suggesting that the metabolic block responsible for this refractoriness was distal to activation of protein kinase. Stimulation of 32Pi incorporation into phospholipid by TSH and acetylcholine was also inhibited during refractoriness. Despite reduction of the stimulatory effect of TSH, binding of 125ITSH was not modified by prior incubation of thyroid slices with TSH. These results indicate that changes in the TSH receptor are not responsible for the development of refractoriness and other metabolic sites besides activation of adenylate cyclase appear to be involved.