Arai M, Tsushima T, Isozaki O, Demura H, Shizume K, Emoto N, Miyakawa M, Nozoe Y, Murakami H, Ohmura E
Institute for Growth Science, Tokyo, Japan.
Eur J Endocrinol. 1995 Feb;132(2):242-8. doi: 10.1530/eje.0.1320242.
Transforming growth factor alpha (TGF-alpha) is a potent mitogen that is similar structurally to epidermal growth factor (EGF). As EGF is a potent growth stimulator and an inhibitor of iodine metabolism in cultured thyroid cells of several species, we studied whether TGF-alpha has similar effects using porcine thyroid cells in culture. Recombinant human TGF-alpha dose-dependently stimulated DNA synthesis of thyroid cells, with maximal stimulation (eight- to ninefold above basal) occurring at 2 nmol/l. The potency was approximately 50% that of mouse EGF and correlated with the ability to compete with EGF for receptor binding, suggesting that the action of TGF-alpha is mediated by interaction with EGF receptors. When thyroid cells were cultured for 3 days with thyrotropin (TSH) in the presence of TGF-alpha, TSH-induced iodide uptake was inhibited in a dose-dependent manner. The potency of TGF-alpha again was approximately 50% that of EGF. Transforming growth factor alpha did not inhibit TSH-stimulated cAMP production. Moreover, iodide uptake stimulated by either forskolin or 8-bromo-cAMP also was inhibited by TGF-alpha. Thus, we conclude that TGF-alpha inhibits TSH-induced iodine metabolism largely by acting at the steps distal to cAMP production. Northern blot analysis revealed expression of TGF-alpha mRNA in porcine thyroid cells. These observations suggest that TGF-alpha acts as an autocrine modulator of growth and differentiated functions in porcine thyroid cells.
转化生长因子α（TGF-α）是一种强效促细胞分裂剂，其结构与表皮生长因子（EGF）相似。由于EGF是几种物种培养的甲状腺细胞中一种强效的生长刺激剂和碘代谢抑制剂，我们使用培养的猪甲状腺细胞研究了TGF-α是否具有类似作用。重组人TGF-α剂量依赖性地刺激甲状腺细胞的DNA合成，在2 nmol/l时出现最大刺激（比基础水平高8至9倍）。其效力约为小鼠EGF的50%，并与与EGF竞争受体结合的能力相关，表明TGF-α的作用是通过与EGF受体相互作用介导的。当甲状腺细胞在TGF-α存在下与促甲状腺激素（TSH）一起培养3天时，TSH诱导的碘摄取以剂量依赖性方式受到抑制。TGF-α的效力再次约为EGF的50%。转化生长因子α不抑制TSH刺激的cAMP产生。此外，由福司可林或8-溴-cAMP刺激的碘摄取也受到TGF-α的抑制。因此，我们得出结论，TGF-α主要通过作用于cAMP产生的远端步骤来抑制TSH诱导的碘代谢。Northern印迹分析显示猪甲状腺细胞中TGF-α mRNA的表达。这些观察结果表明，TGF-α在猪甲状腺细胞中作为生长和分化功能的自分泌调节剂发挥作用。
