Grimes R W, Hammond J M
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Endocrinology. 1992 Aug;131(2):553-8. doi: 10.1210/endo.131.2.1379161.
Ligand blot analysis of granulosa cell (GC)-conditioned culture medium revealed several easily measurable insulin-like growth factor (IGF)-binding proteins (IGFBPs), including IGFBP-3 [40-44 kilodaltons (kDa)] and IGFBP-2 (34 kDa). In the present study, IGF-I, in a dose-dependent manner, significantly stimulated the production of these IGFBPs. Insulin, but not IGF-II, mimicked IGF-I's action on IGFBP-3 and -2 production, but was less potent. The synthetic IGF, long R3-IGF-I, which has very low affinity for IGFBPs and only slightly reduced affinity for the IGF-I (type I) receptor, had significantly greater potency in stimulating IGFBP-3 and -2 production compared to IGF-I. Des-(1-3)-IGF-I had similar effects. IGF-I, IGF-II, and the IGF-I analogs, but not insulin, also induced production of an unidentified 30-kDa IGFBP not normally detectable in these cultures. However, in the presence of epidermal growth factor (which was without independent effect on the 30-kDa IGFBP), insulin also induced this 30-kDa IGFBP. By Northern analysis the expression of IGFBP-3 mRNA was found to be significantly stimulated by IGF-I. In summary, insulin stimulated IGFBP-3 and -2 production in a manner that mimics that of IGF-I and the more potent long R3-IGF-I. However, its low potency suggested that IGFBP production is regulated via the IGF-I (type I) receptor. The much higher potency of long R3-IGF-I compared to that of IGF-I suggests that the IGFBPs themselves modulate the action of IGFs by sequestering exogenous IGFs. Thus, one cellular response to IGF stimulation is the production of IGFBPs, which, in turn, reduce or negate the biological activity of the IGFs. The effects of insulin-like peptides are exerted at least in part by increasing levels of mRNA for specific BPs.
颗粒细胞（GC）条件培养基的配体印迹分析显示了几种易于检测的胰岛素样生长因子（IGF）结合蛋白（IGFBPs），包括IGFBP - 3[40 - 44千道尔顿（kDa）]和IGFBP - 2（34 kDa）。在本研究中，IGF - I以剂量依赖性方式显著刺激了这些IGFBPs的产生。胰岛素，但不是IGF - II，模拟了IGF - I对IGFBP - 3和 - 2产生的作用，但效力较低。合成的IGF，长R3 - IGF - I，对IGFBPs的亲和力非常低，对IGF - I（I型）受体的亲和力仅略有降低，与IGF - I相比，在刺激IGFBP - 3和 - 2产生方面具有显著更高的效力。脱（1 - 3）- IGF - I具有类似的效果。IGF - I、IGF - II和IGF - I类似物，但不是胰岛素，也诱导了一种在这些培养物中通常无法检测到的未鉴定的30 kDa IGFBP的产生。然而，在存在表皮生长因子（其对30 kDa IGFBP无独立作用）的情况下，胰岛素也诱导了这种30 kDa IGFBP。通过Northern分析发现，IGF - I显著刺激了IGFBP - 3 mRNA的表达。总之，胰岛素以模拟IGF - I和效力更强的长R3 - IGF - I的方式刺激了IGFBP - 3和 - 2的产生。然而，其低效力表明IGFBP的产生是通过IGF - I（I型）受体调节的。长R3 - IGF - I与IGF - I相比效力高得多，这表明IGFBPs本身通过螯合外源性IGFs来调节IGFs的作用。因此，细胞对IGF刺激的一种反应是产生IGFBPs，这反过来又降低或消除了IGFs的生物活性。胰岛素样肽的作用至少部分是通过增加特定BP的mRNA水平来发挥的。
