Gabillard Jean-Charles, Kamangar Barzan Bahrami, Montserrat Nuria
Institut National de la Recherche Agronomique, INRA - SCRIBE, IFR 140, Campus Beaulieu, 35000 Rennes, France.
J Endocrinol. 2006 Oct;191(1):15-24. doi: 10.1677/joe.1.06869.
The GH/IGF system is a complex regulation network strongly dependent on nutrient availability. While the effect of starvation on the GH/IGF system has been extensively studied, the time course of events leading to the restoration of GH/IGF system activity after starvation is largely unknown. We, therefore, measured the plasma levels of GH, IGF-I and IGF-II and the expression of the GH/IGF system in liver and muscle. Starvation increased the plasma GH level and 1 day of refeeding completely restored it (1.10 +/- 0.27 vs 1.12 +/- 0.28 ng/ml). Thereafter, plasma GH continued to decrease until day 7 and returned to control values from day 15. Starvation decreased plasma IGF-I and IGF-II and refeeding raised plasma IGF-I only from day 4. In contrast, the plasma IGF-II level doubled after 1 day's refeeding (26.5 +/- 1.9 vs 44.0 +/- 3.4 ng/ml; P < 0.01). Starved fish exhibited higher GH receptor (GHR)1 mRNA abundance in liver and muscle than in controls, whereas GHR2 mRNA abundance was increased only in muscle. In liver, 1 day of refeeding, decreased GHR1 (twofold), but increased GHR2 mRNA abundance (twofold). Thereafter, a progressive return to normal values was observed. Liver IGFBP-4 mRNA abundance was lowered in starved fish followed by a progressive restoration during refeeding. Starvation had no effect on liver IGFBP-2 and IGFBP-6 mRNA abundance, whereas refeeding provoked a peak of IGFBP-2 and IGFBP-6 expression at day 7. In muscle, starvation led to a decrease of the IGFBP-2 mRNA level, which was restored only from day 7. IGFBP-4 mRNA abundance in starved fish was lower than in the controls and refeeding led to a transient upregulation (sevenfold) of IGFBP-4 gene at day 1. IGF-I, IGFBP-5, and IGFBP-related protein 1 (rP1) expression profiles were similar, showing a decrease of expression after starvation, a first peak of expression at day 2, a second peak at day 7, and a return to normal value from day 15. Moreover, IGF-I, IGFBP-5, and IGFBP-rP1 mRNA abundance were positively correlated (r = 0.6-0.8; P < 0.0001). In conclusion, plasma IGF-I was restored later than plasma GH level, which suggests that plasma IGF-I levels cannot account for plasma GH changes. The coordinated regulation of IGF-I, IGFBP-5, and IGFBP-rP1 expression would be a signature for the resumption of myogenic activity.
生长激素/胰岛素样生长因子（GH/IGF）系统是一个高度依赖营养物质供应的复杂调控网络。虽然饥饿对GH/IGF系统的影响已得到广泛研究，但饥饿后导致GH/IGF系统活性恢复的事件时间进程在很大程度上尚不清楚。因此，我们测量了血浆中生长激素（GH）、胰岛素样生长因子-I（IGF-I）和胰岛素样生长因子-II（IGF-II）的水平以及肝脏和肌肉中GH/IGF系统的表达。饥饿使血浆GH水平升高，1天的再投喂使其完全恢复（1.1±0.27对1.12±0.28 ng/ml）。此后，血浆GH持续下降直至第7天，并从第15天起恢复到对照值。饥饿使血浆IGF-I和IGF-II水平降低，再投喂仅从第4天起使血浆IGF-I升高。相反，再投喂1天后血浆IGF-II水平翻倍（26.5±1.9对44.0±3.4 ng/ml；P<0.01）。饥饿的鱼肝脏和肌肉中的生长激素受体（GHR）1 mRNA丰度高于对照组，而GHR2 mRNA丰度仅在肌肉中增加。在肝脏中，再投喂1天使GHR1（两倍）降低，但使GHR2 mRNA丰度增加（两倍）。此后，观察到逐渐恢复到正常值。饥饿鱼肝脏中胰岛素样生长因子结合蛋白-4（IGFBP-4）mRNA丰度降低，再投喂期间逐渐恢复。饥饿对肝脏IGFBP-2和IGFBP-6 mRNA丰度无影响，而再投喂在第7天引发IGFBP-2和IGFBP-6表达峰值。在肌肉中，饥饿导致IGFBP-2 mRNA水平降低，仅从第7天起恢复。饥饿鱼中IGFBP-4 mRNA丰度低于对照组，再投喂在第1天导致IGFBP-4基因瞬时上调（七倍）。IGF-I、IGFBP-5和胰岛素样生长因子结合蛋白相关蛋白1（rP1）的表达谱相似，显示饥饿后表达降低，第2天出现第一个表达峰值，第7天出现第二个峰值，从第15天起恢复到正常值。此外，IGF-I、IGFBP-5和IGFBP-rP1 mRNA丰度呈正相关（r = 0.6 - 0.8；P<0.0001）。总之，血浆IGF-I的恢复晚于血浆GH水平，这表明血浆IGF-I水平不能解释血浆GH的变化。IGF-I、IGFBP-5和IGFBP-rP1表达的协同调控将是肌生成活性恢复的标志。
