Ealey P A, Ahene C A, Emmerson J M, Marshall N J
Department of Chemical Pathology, University College Hospital, London.
J Endocrinol. 1987 Aug;114(2):199-205. doi: 10.1677/joe.0.1140199.
The adenylate cyclase stimulator forskolin increases intracellular cyclic AMP (cAMP) in rat FRTL-5 cells within minutes and, after a lag phase of 20-24 h, an increase of cells in metaphase is seen. The dose-response relationships were similar in both systems, with significant increases in the number of metaphases observed at approximately 0.1 mumol/l and a doubling of cAMP levels at 1 mumol/l, whilst doses of 0.1 mmol/l and above proved cytotoxic. An involvement of intracellular cAMP as a positive intermediate in cell division was further suggested by the finding that a low dose of forskolin (0.1 mumol/l) potentiated TSH stimulation of mitosis. Isobutyl methyl xanthine (IBMX), a phosphodiesterase inhibitor, also acted as a mitogen and potentiated TSH action. Moreover, the simultaneous inclusion of low doses of IBMX and forskolin additionally potentiated TSH stimulation of mitosis. An analogue of cAMP, dibutyryl cAMP, also stimulated mitosis and acted over a restricted dose range, with maximal stimulation at 1 mmol/l. We conclude that cAMP may act as a positive signal for FRTL-5 thyroid cell proliferation.
腺苷酸环化酶刺激剂福斯高林在数分钟内就能提高大鼠FRTL-5细胞内的环磷酸腺苷（cAMP）水平，并且在20 - 24小时的延迟期后，可见中期细胞数量增加。两个系统中的剂量反应关系相似，在约0.1 μmol/l时观察到中期细胞数量显著增加，在1 μmol/l时cAMP水平翻倍，而0.1 mmol/l及以上的剂量则具有细胞毒性。低剂量福斯高林（0.1 μmol/l）增强促甲状腺激素（TSH）对有丝分裂的刺激作用这一发现，进一步表明细胞内cAMP作为细胞分裂中的一种正向中间体发挥作用。磷酸二酯酶抑制剂异丁基甲基黄嘌呤（IBMX）也可作为有丝分裂原并增强TSH的作用。此外，同时加入低剂量的IBMX和福斯高林可进一步增强TSH对有丝分裂的刺激作用。cAMP的类似物二丁酰cAMP也能刺激有丝分裂，且作用于有限的剂量范围，在1 mmol/l时刺激作用最强。我们得出结论，cAMP可能作为FRTL-5甲状腺细胞增殖的正向信号。
