Conover C A, Clarkson J T, Bale L K
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905.
Endocrinology. 1995 Apr;136(4):1403-10. doi: 10.1210/endo.136.4.7534698.
Insulin-like growth factor (IGF)-binding proteins (IGFBPs) can determine IGF biological competence at the cellular level. IGF-I itself has been shown to be an important peptide regulator of local IGFBP availability. Glucocorticoid also has major effects on IGFBP expression. In the present study, we assessed integrated IGF-I and glucocorticoid regulation of IGFBP messenger RNA (mRNA) and protein expression in two fibroblast model systems. In bovine fibroblasts, IGF-I treatment induced IGFBP-3 and IGFBP-5 mRNA and protein secretion, and had a moderate effect on IGFBP-4 expression. Dexamethasone had little effect on the IGF-induced increase in IGFBP-3, but completely blocked the increase in IGFBP-5 expression. Basal IGFBP-4 expression was inhibited by dexamethasone, and this effect was counteracted by IGF-I. IGFBP-2 expression did not vary with IGF-I or dexamethasone treatment in these cells; IGFBP-1 mRNA was not detectable, and IGFBP-6 mRNA was low and inconsistent. In human fibroblasts, IGF-I treatment increased levels of IGFBP-3 and decreased levels of IGFBP-4 without influencing mRNA expression. IGF-I also increased steady state levels of IGFBP-5 mRNA. Dexamethasone alone decreased IGFBP-3, IGFBP-4, and IGFBP-5 mRNA, but it had no significant effect on IGFBP-3, -4, or -5 expression in the presence of IGF-I. Human fibroblast IGFBP-6 expression was stable under the different culture conditions; IGFBP-1 and -2 mRNA were not detected. These data demonstrate that IGF peptide and glucocorticoid individually modulate IGFBP expression and indicate that glucocorticoid has distinct effects on IGF regulation of IGFBP depending upon the particular IGFBP and the underlying mechanism of IGF regulation. Bovine fibroblasts may provide a useful model system to probe the molecular mechanisms of IGFBP-3, -4, and -5 gene expression and regulation by IGF-I and glucocorticoid, whereas human fibroblasts may be suitable for studying posttranscriptional interactions.
胰岛素样生长因子（IGF）结合蛋白（IGFBPs）可在细胞水平上决定IGF的生物学活性。IGF-I本身已被证明是局部IGFBP可用性的重要肽调节剂。糖皮质激素对IGFBP表达也有主要影响。在本研究中，我们在两种成纤维细胞模型系统中评估了IGF-I和糖皮质激素对IGFBP信使核糖核酸（mRNA）和蛋白表达的综合调节作用。在牛成纤维细胞中，IGF-I处理可诱导IGFBP-3和IGFBP-5 mRNA及蛋白分泌，并对IGFBP-4表达有中等程度的影响。地塞米松对IGF诱导的IGFBP-3增加影响不大，但完全阻断了IGFBP-5表达的增加。地塞米松抑制基础IGFBP-4表达，而这种作用被IGF-I抵消。在这些细胞中，IGFBP-2表达不随IGF-I或地塞米松处理而变化；未检测到IGFBP-1 mRNA，且IGFBP-6 mRNA水平较低且不稳定。在人成纤维细胞中，IGF-I处理可增加IGFBP-3水平并降低IGFBP-4水平，而不影响mRNA表达。IGF-I还增加了IGFBP-5 mRNA的稳态水平。单独使用地塞米松可降低IGFBP-3、IGFBP-4和IGFBP-5 mRNA，但在有IGF-I存在时，它对IGFBP-3、-4或-5表达无显著影响。人成纤维细胞IGFBP-6表达在不同培养条件下稳定；未检测到IGFBP-1和-2 mRNA。这些数据表明，IGF肽和糖皮质激素分别调节IGFBP表达，并表明糖皮质激素对IGF调节IGFBP具有不同影响，这取决于特定的IGFBP和IGF调节的潜在机制。牛成纤维细胞可能是探究IGF-I和糖皮质激素对IGFBP-3、-4和-5基因表达及调节的分子机制的有用模型系统，而人成纤维细胞可能适合研究转录后相互作用。
