Hypothyroidism and hyperthyroidism modulates Ras-MAPK intracellular pathway in rat thyroids
Hypothyroidism and hyperthyroidism modulates Ras-MAPK intracellular pathway in rat thyroids
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DOI：
10.1007/s12020-007-0029-4
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发表时间：
2007-04-01
期刊：
影响因子：
3.7
通讯作者：
da Costa, Vania Maria Correa
中科院分区：
文献类型：
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作者：
Leal, Anna Lucia R. C.;Pantaleao, Thiago U.;da Costa, Vania Maria Correa
促甲状腺激素通过七跨膜G蛋白偶联受体诱导甲状腺细胞增殖和功能。促甲状腺激素（TSH）在体内诱导甲状腺细胞增殖的途径尚不完全清楚。本工作的目的是评估，如果Ras可以诱导TSH在大鼠甲状腺，以及是否细胞外调节激酶（ERK）可能参与随后的细胞内信号级联。我们用甲巯咪唑（MMI）处理Wistar大鼠（0.03%饮水21天）诱发甲状腺功能减退症。在MMI治疗的最后10天，甲状腺功能减退大鼠的一个亚组接受T-4（1 μ g/100 g bw）。在另一组大鼠中，通过皮下注射T-4（10 μ g/100 g bw）诱导甲状腺功能亢进症，持续10天。我们的数据表明，在甲状腺功能减退大鼠有一个明确的积极的Ras调制，但减少pERK。相反，甲状腺pERK增加T-4诱导的甲状腺功能亢进症，但没有任何变化，RAS，虽然这些变化没有达到统计学意义。因此，虽然TSH诱导的大鼠甲状腺增殖可能涉及RAS信号传导的增加，但随后的级联反应不涉及ERK磷酸化，而ERK磷酸化实际上在T-4诱导的甲状腺功能亢进症期间增加。
Thyrotrophin induces proliferation and function in thyroid cells acting through a seven transmembrane G protein-coupled receptor. The proliferative pathways induced by thyrotropin (TSH) in thyrocytes in vivo are not completely understood yet. The aim of this work is to evaluate if Ras can be induced by TSH in rat thyroids, and whether extracellular regulated kinase (ERK) may be involved in the subsequent intracellular signalling cascade. We induced hypothyroidism in Wistar rats by methimazole (MMI) treatment (0.03% in the drinking water for 21 days). A subset of the hypothyroid rats received T-4 (1 mu g/100 g bw) during the last 10 days of MMI treatment. Hyperthyroidism was induced by subcutaneous injections of T-4 (10 mu g/100 g bw) during 10 days in another group of rats. Our data show that in the hypothyroid rats there is a clear positive Ras modulation, but a decrease in pERK. In contrast, thyroidal pERK increases in T-4-induced hyperthyroidism, but without any change in RAS, although these changes did not reach statistical significance. Thus, while the rat thyroid proliferation induced by TSH may involve an increase in RAS signalling, the subsequent cascade does not involve ERK phosphorilation, which in fact, increases during T-4-induced hyperthyroidism.