Møller S, Juul A, Becker U, Flyvbjerg A, Skakkebaek N E, Henriksen J H
Department of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, University of Copenhagen, Denmark.
J Clin Endocrinol Metab. 1995 Apr;80(4):1148-57. doi: 10.1210/jcem.80.4.7536200.
The liver is thought to be the major source of circulating insulin-like growth factor (IGF-I) and IGF-binding protein-1 (IGFBP-1), whereas the primary production site of circulating IGFBP-3 remains unknown. As other tissues may contribute to the circulating pool of IGF-I and IGFBP, the aim of the present study was to assess the hepatic and renal arterio-venous difference and production rates of IGF-I, IGFBP-1, IGFBP-3, and GH in cirrhotic patients (n = 22) and matched control subjects (n = 27). IGFBP-1 and -3, IGF-I, and GH levels were measured by RIA in hepatic, renal, and peripheral veins and in the femoral artery. Levels of IGFBP-1 to -4 were additionally determined by Western ligand blotting. Hepatic venous IGFBP-1 was significantly increased in the cirrhotic patients (mean +/- SEM, 33.6 +/- 9.1 vs. 10.4 +/- 1.9 micrograms/L; P < 0.001), and arterio-renal-venous extraction was significant in both patients (6 +/- 2%; P < 0.01) and controls (11 +/- 1%; P < 0.001). Conversely, IGFBP-3 was decreased in the cirrhotic patients (1265 +/- 149 vs. 2712 +/- 137 micrograms/L; P < 0.001). IGFBP-3 correlated significantly with the wedged hepatic venous pressure (r = -0.49; P < 0.05), serum aspartate aminotransferase (r = -0.66; P < 0.01), serum bilirubin (r = -0.65; P < 0.01), serum albumin (r = 0.64; P < 0.01), and the Child score (r = -0.57; P < 0.01). IGF-I was significantly lower in the cirrhotics (57 +/- 10 vs. 143 +/- 11 micrograms/L; P < 0.001). No significant IGFBP-3 proteolysis was demonstrated in cirrhotics or controls. No significant differences were found in the values obtained simultaneously from hepatic, renal, and brachial veins or femoral artery, which suggests that no major net production or release of IGFBP-3 or IGF-I occurs in these tissues. No differences in IGFBP-2 or IGFBP-4 determined by Western ligan blot were found between patients and controls. The IGF-I concentrations correlated significantly with parameters of biochemical liver function. Basal GH concentrations were significantly higher in the cirrhotics (1.19 +/- 0.13 vs. 0.58 +/- 0.08 micrograms/L; P < 0.001). A significant hepatic disposal of GH was found in the patients (P < 0.05) and controls (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
肝脏被认为是循环中胰岛素样生长因子（IGF-I）和IGF结合蛋白-1（IGFBP-1）的主要来源，而循环中IGFBP-3的主要产生部位尚不清楚。由于其他组织可能对循环中的IGF-I和IGFBP有贡献，本研究的目的是评估肝硬化患者（n = 22）和匹配的对照受试者（n = 27）肝脏和肾脏的动静脉差异以及IGF-I、IGFBP-1、IGFBP-3和生长激素（GH）的产生率。通过放射免疫分析法（RIA）测定肝静脉、肾静脉、外周静脉和股动脉中IGFBP-1和-3、IGF-I以及GH的水平。另外通过Western配体印迹法测定IGFBP-1至-4的水平。肝硬化患者肝静脉中的IGFBP-1显著升高（均值±标准误，33.6±9.1 vs. 10.4±1.9μg/L；P < 0.001），患者（6±2%；P < 0.01）和对照组（11±1%；P < 0.001）的动-肾-静脉提取均显著。相反，肝硬化患者的IGFBP-3降低（1265±149 vs. 2712±137μg/L；P < 0.001）。IGFBP-3与肝静脉楔压（r = -0.49；P < 0.05）、血清天冬氨酸转氨酶（r = -0.66；P < 0.01）、血清胆红素（r = -0.65；P < 0.01）、血清白蛋白（r = 0.64；P < 0.01）以及Child评分（r = -0.57；P < 0.01）显著相关。肝硬化患者的IGF-I显著降低（57±10 vs. 143±11μg/L；P < 0.001）。在肝硬化患者或对照组中均未证实有显著的IGFBP-3蛋白水解。从肝静脉、肾静脉、肱静脉或股动脉同时获得的值没有显著差异，这表明这些组织中没有IGFBP-3或IGF-I的主要净产生或释放。患者和对照组之间通过Western配体印迹法测定的IGFBP-2或IGFBP-4没有差异。IGF-I浓度与肝脏生化功能参数显著相关。肝硬化患者的基础GH浓度显著更高（1.19±0.13 vs. 0.58±0.08μg/L；P < 0.001）。在患者（P < 0.05）和对照组（P < 0.001）中均发现有显著的肝脏GH清除。（摘要截断于400字）
