Saunier B, Tournier C, Jacquemin C, Pierre M
Unité 96, INSERM, Le Kremlin-Bicêtre, France.
J Biol Chem. 1995 Feb 24;270(8):3693-7. doi: 10.1074/jbc.270.8.3693.
In the thyroid, thyrotropin (TSH) stimulates both growth and function, and stimulates the production of cAMP which reproduces most of the effects of TSH. Here, we report evidence that TSH stimulates the mitogen-activated protein (MAP) kinase cascade through a cAMP-independent pathway, in human thyroid. TSH stimulated MAP kinase activity (4-9-fold the basal level) measured in the cytosolic fractions of primary cultured thyroid follicles. Maximal activity was reached after 20 min and remained sustained for 1-3 h, TSH being as potent as EGF; EC50 was 1.5 nM TSH. Only a single isoform of MAP kinase (p42) was detected in the follicles. p42 was phosphorylated on tyrosine residues and showed a reduced electrophoretic mobility in follicles stimulated by TSH. All these effects on MAP kinase were decreased by preincubation of the follicles with human anti-TSH receptor antibodies. The stimulation of MAP kinase by TSH was neither blocked by pertussis toxin nor reproduced by forskolin, cholera toxin, or 8-bromo-cAMP. In conclusion, in human thyroid cells, in contrast with previous observations on dog thyroid cells, TSH stimulates strongly MAP kinase through a pertussis toxin-insensitive and cAMP-independent pathway.
在甲状腺中，促甲状腺激素（TSH）刺激生长和功能，并刺激环磷酸腺苷（cAMP）的产生，而cAMP可重现TSH的大部分作用。在此，我们报告证据表明，在人甲状腺中，TSH通过一条不依赖cAMP的途径刺激丝裂原活化蛋白（MAP）激酶级联反应。TSH刺激原代培养的甲状腺滤泡胞质部分中测得的MAP激酶活性（为基础水平的4 - 9倍）。20分钟后达到最大活性，并持续1 - 3小时，TSH与表皮生长因子（EGF）一样有效；半数有效浓度（EC50）为1.5 nM TSH。在滤泡中仅检测到一种MAP激酶同工型（p42）。p42在酪氨酸残基上被磷酸化，并且在TSH刺激的滤泡中电泳迁移率降低。用人抗TSH受体抗体预孵育滤泡可降低所有这些对MAP激酶的影响。TSH对MAP激酶的刺激既不被百日咳毒素阻断，也不能被福斯可林、霍乱毒素或8 - 溴 - cAMP重现。总之，在人甲状腺细胞中，与先前对犬甲状腺细胞的观察结果相反，TSH通过一条对百日咳毒素不敏感且不依赖cAMP的途径强烈刺激MAP激酶。
