REGULATION OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) AND IGF-BINDING PROTEINS BY TUMOR-NECROSIS-FACTOR
REGULATION OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) AND IGF-BINDING PROTEINS BY TUMOR-NECROSIS-FACTOR
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DOI：
10.1152/ajpregu.1995.269.5.r1204
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发表时间：
1995-11-01
影响因子：
2.8
通讯作者：
LANG, CH
中科院分区：
文献类型：
--
作者：
FAN, J;CHAR, D;LANG, CH
本研究的目的是确定1）外源性给予肿瘤坏死因子-α（TNF-α）是否改变胰岛素样生长因子-I（IGF-I）和IGF结合蛋白（BP），以及2）TNF的内源性产生是否介导脂多糖（LPS）诱导的IGF系统变化。小鼠TNF-α的过夜输注降低了禁食大鼠中生长激素（GH）和IGF-I的循环浓度。此外，TNF-α降低肝脏、腓肠肌和垂体中IGF-I的含量。相反，TNF-α增加肾脏和大脑中IGF-I的含量。IGFBP-1在血浆、肝脏和肌肉中增加，以响应TNF-α。在第二项研究中，在用中和性抗TNF抗体（Ab）处理后给大鼠注射LPS，并在4小时后收集血液和组织。在LPS处理的大鼠中，GH和IGF-I的血浆浓度降低。LPS还降低了肝脏和骨骼肌中IGF-I的含量，并增加了血浆、肝脏和肌肉中IGFBP-1的浓度。用抗TNF抗体预处理减弱了LPS诱导的血浆和肝脏中IGF-I的降低和IGFBP-1的增加，并完全阻止了在肌肉中观察到的IGF-I的降低。相反，LPS诱导的血浆GH减少和肌肉中观察到的IGFBP-1增加未被抗TNF Ab改变。这些结果表明，GH/IGF轴对TNF-α敏感，TNF的内源性产生增强介导了血浆、肝脏和肌肉中LPS诱导的IGF-I降低的主要部分，以及血浆和肝脏中IGFBP-1伴随升高的较小部分。
The purpose of the present study was to determine 1) whether exogenous administration of tumor necrosis factor-alpha (TNF-alpha) alters insulin-like growth factor-I (IGF-I) and IGF-binding proteins (BPs) and 2) whether the enhanced endogenous production of TNF mediates the lipopolysaccharide (LPS)-induced changes in the IGF system. The overnight infusion of murine TNF-alpha reduced circulating concentrations of both growth hormone (GH) and IGF-I in fasted rats. Furthermore, TNF-alpha decreased IGF-I content in liver, gastrocnemius muscle, and pituitary. In contrast, TNF-alpha increased IGF-I content in kidney and brain. IGFBP-1 was increased in plasma, liver, and muscle in response to TNF-alpha. In a second study, rats were injected with LPS after treatment with a neutralizing anti-TNF antibody (Ab), and blood and tissues were collected 4 h later. In LPS-treated rats, plasma concentrations of GH and IGF-I were reduced. LPS also decreased the IGF-I content in liver and skeletal muscle and increased plasma, liver, and muscle concentrations of IGFBP-1. Pretreatment with anti-TNF Ab attenuated the LPS-induced reduction in IGF-I and the increased IGFBP-1 in plasma and Liver and completely prevented the decrease in IGF-I observed in muscle. In contrast, the LPS-induced decrease in plasma GH and the increased IGFBP-1 observed in muscle were unaltered by the anti-TNF Ab. These results indicate that the GH/IGF axis is sensitive to TNF-alpha and that enhanced endogenous production of TNF mediates a major portion of the LPS-induced decrease in IGF-I in plasma, liver, and muscle, as well as a smaller portion of the concomitant elevation in IGFBP-1 in plasma and liver.