Coordinated regulation of the GH/IGF system genes during refeeding in rainbow trout (Oncorhynchus mykiss)

Abstract

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.