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首页> 外文期刊>Journal of Cellular Physiology >Differential effects of glucocorticoids on insulin-like growth factor I action in cultured human fibroblasts.
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Differential effects of glucocorticoids on insulin-like growth factor I action in cultured human fibroblasts.

机译：微分的影响糖皮质激素胰岛素样生长因子在培养我行动人类成纤维细胞。

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摘要

Glucocorticoids act synergistically with insulin-like growth factor I (IGF-I) to stimulate DNA synthesis and replication of cultured human fibroblasts. In the present study, we further define glucocorticoid and IGF-I interactive effects on human fibroblast metabolism and growth. IGF-I stimulated dose-dependent increases in early metabolic events. Half-maximal effectiveness was seen at 5-8 ng/ml IGF-I, with mean maximal responses of 1.5-, 2-, and 6-fold for [3H]2-deoxyglucose uptake, [14C]glucose incorporation, and [14C]aminoisobutyric acid (AIB) uptake, respectively. A 48-hour preincubation with 10(-7) M dexamethasone markedly enhanced both the sensitivity and maximal effectiveness of IGF-I stimulation of AIB uptake. In contrast, dexamethasone had no effect on IGF-I-stimulated glucose uptake and utilization. Maximum specific binding of [125I]IGF-I to fibroblast monolayers was identical in ethanol control and glucocorticoid-treated cells, with 50% displacement at approximately 5 ng/ml IGF-I. In additionto its synergism with IGF-I, preincubation with dexamethasone augmented insulin and epidermal growth factor (EGF) stimulation of [3H]thymidine incorporation; dexamethasone had no effect on platelet-derived growth factor or fibroblast growth factor action. Two-dimensional gel electrophoresis identified two specific glucocorticoid-induced proteins in human fibroblast cell extracts with molecular weights of 45K and 53K and pIs of 6.8 and 6.3, respectively. These data indicate that IGF-I receptor-mediated actions in human fibroblasts are differentially modulated by glucocorticoids. Glucocorticoids are synergistic with IGF-I in stimulating mitogenesis and amino acid uptake, without having any apparent effect on IGF-I-stimulating glucose metabolism. Glucocorticoid enhancement of growth factor bioactivity may involve modulation of a regulatory event in the mitogenic signaling pathway subsequent to cell surface receptor activation.
机译：糖皮质激素协同作用与胰岛素样生长因子I (IGF-I)刺激培养人的DNA合成和复制成纤维细胞。定义糖皮质激素和IGF-I互动对人类成纤维细胞的新陈代谢和影响增长。在早期的代谢活动。有效性是在5 - 8 ng / ml IGF-I,平均最大响应1.5,2 - 6倍[3 h] 2-deoxyglucose吸收,[14 c]葡萄糖公司,[14 c] aminoisobutyric酸分别(AIB)吸收。预培养10 M地塞米松(7)显著增强敏感性和爱尔兰联合银行的最大的有效性IGF-I刺激吸收。IGF-I-stimulated葡萄糖摄取和的利用率。[125 i] IGF-I单层成纤维细胞相同的控制和乙醇glucocorticoid-treated细胞,为50%在大约5 ng / ml IGF-I位移。外与IGF-I合作,预培养与地塞米松增强胰岛素和表皮生长因子(EGF)刺激[3 h]胸腺嘧啶核苷掺入;地塞米松对血小板源没有影响生长因子或纤维母细胞生长因子的行动。二维凝胶电泳鉴定在两个特定激素性蛋白质人类成纤维细胞与分子细胞提取物体重45 k和53的6.8和6.3 k和π,分别。人类成纤维细胞受体介导的行动由糖皮质激素不同调制。糖皮质激素与IGF-I协同促进有丝分裂发生和氨基酸的摄取。没有任何明显的影响IGF-I-stimulating葡萄糖代谢。糖皮质激素增强经济增长的因素生物活性可能涉及的调制监管活动促有丝分裂的信号细胞表面受体通路后续激活。

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