Demonstration of the production and physiological role of insulin-like growth factor II in rat thyroid follicular cells in culture.

Demonstration of the production and physiological role of insulin-like growth factor II in rat thyroid follicular cells in culture.
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演示培养的大鼠甲状腺滤泡细胞中胰岛素样生长因子 II 的产生和生理作用。

DOI:
10.1172/jci113764
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发表时间:
1988
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Ingbar,SH
Ingbar,SH
中科院分区:
--
文献类型:
--
作者:
Maciel,RM;Moses,AC;Villone,G;Tramontano,D;Ingbar,SH

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胰岛素样生长因子(IGFs)是FRTL5大鼠甲状腺滤泡细胞的有效丝裂原。IGFs还协同促甲状腺激素(TSH)和其他增加细胞内AMP浓度的药物的独立有丝分裂作用。我们检测了FRTL5细胞和由其衍生的tsh非依赖性突变细胞系M12细胞是否分泌调节大鼠甲状腺滤泡细胞生长的IGF。在由FRTL5细胞调节的培养基中发现了免疫反应性IGF-II,而不是IGF-I;M12细胞培养基的浓度高出4 - 5倍。由FRTL5和M12调节的培养基均刺激了FRTL5中[3H]胸腺嘧啶的掺入,并增强了TSH的有丝分裂作用。m12条件培养基比frtl5条件培养基更有效。Sm-1.2是一种识别IGF- i和IGF- ii但不识别胰岛素的单克隆抗体,可抑制FRTL5和M12细胞的基础DNA合成以及与IGF协同作用的药物(如TSH、forskolin、Bt2cAMP和Graves'-IgG)在FRTL5中的有丝分裂作用。Sm-1.2不抑制有丝分裂对胰岛素的反应。因此,大鼠胰岛素样生长因子II (rIGF-II)是一种调节FRTL5生长的自分泌生长因子,部分通过放大对TSH的有丝分裂反应。M12细胞的结果提出了内源性rIGF-II可能部分介导这些细胞不依赖于tsh的生长的可能性。
Insulin-like growth factors (IGFs) are potent mitogens for FRTL5 rat thyroid follicular cells. IGFs also synergize the independent mitogenic effects of thyrotropin-stimulating hormone (TSH) and other agents that increase intracellular AMP concentration. We examined whether FRTL5 cells and M12 cells, a TSH-independent mutant cell line derived therefrom, secrete IGF that regulates the growth of rat thyroid follicular cells. Immunoreactive IGF-II, but not IGF-I, was found in media conditioned by FRTL5 cells; media from M12 cells contained four- to fivefold higher concentrations. Medium conditioned by FRTL5 and M12 both stimulated [3H]thymidine incorporation in FRTL5 and amplified the mitogenic effects of TSH. M12-conditioned medium was more potent than FRTL5-conditioned medium. Sm-1.2, a monoclonal antibody that recognizes IGF-I and IGF-II but not insulin, inhibited basal DNA synthesis in FRTL5 and M12 cells and the mitogenic effects in FRTL5 of agents that are synergized by IGF, such as TSH, forskolin, Bt2cAMP, and Graves'-IgG. Sm-1.2 did not inhibit the mitogenic response to insulin. Thus, rat insulin-like growth factor II (rIGF-II) is an autocrine growth factor that regulates FRTL5 growth, in part by amplifying the mitogenic response to TSH. Results with M12 cells raise the possibility that endogenous rIGF-II may partially mediate the TSH-independent growth of these cells.