Ontogenic differences in the nutritional regulation of circulating IGF binding proteins in sheep plasma

Abstract

Well-fed castrated male sheep (N= 3) and 125 days gestation pregnant ewes (N = 6) with chronically catheterized fetuses were fasted for 72 h. Insulin-like growth factor-binding protein (IGFBP) levels in fed and starved fetal, maternal and castrated male sheep plasma were measured using ligand blot analysis. IGFBPs in adult and fetal sheep differed in distribution both before and after 72 h starvation. IGFBP-3 was the major postnatal binding protein, while in the fetus IGFBP-2, IGFBP-3 and the circulating IGF type 2 receptor fragment each contributed 2 5–30% of total IGF binding capacity. After starvation, total IGF binding capacity and IGFBP-3 fell in plasma of maternal and castrated male sheep (p<0.05). Total IGF binding capacity rose with starvation in fetal plasma (p <0.05) as a result of an increase in IGFBP-1 (p< 0.01) and IGFBP-2 (p<0.05). The different nutritional control of the IGFBPs in the fetus and the adult may reflect ontogenic differences in the regulation and function of circulating IGFs and their binding proteins.

Nutritional programming: prenatal nutritional effects on the regulation of growth and metabolism

“…Maternal undernutrition increases foetal IGFBP-1 and IGFBP-2 while IGFBP-3 concentration is decreased (Gallaher et al, 1992(Gallaher et al, , 1994. Similar results have been reported by El-Khattabi et al (2003) with maternal low protein diet suggesting a modulation of IGF-1 biologic activity by IGF binding proteins.…”

Effect of feed restriction on serum somatotropin, insulin-like growth factor-I-(IGF-I) and IGF binding proteins in cyclic heifers actively immunized against growth hormone releasing factor

“…Other reports have failed to show a clear effect of feed restriction on IGFBP in ruminants (5); however, Vincini (39) reported that IGFBP-2 was higher during early lactation when cows were in negative energy balance. Gallaher (10) found that fasting castrate sheep decreased IGFBP-3 and increased IGFBP-2; however, fast ing in pregnant ewes was associated with a slight decrease in IGFBP-3, but no change in IGFBP-2. Although markedly affected by GRFi, both concentrations of IGFBP-3 (estimated by ligand blot) and IGFBP-2 (estimated by RIA) were not significantly altered by feed re striction.…”

“…The IGFs circulate bound to specific, high affinity binding proteins (IGFBP) which modu late their activity. Serum IGFBP have been shown to be altered by feed restriction in neo natal pigs, rats and humans (4,7,8,9); however, data in ruminants is limited (5,10).…”

Chronic pulsatile infusion of growth hormone to growth-restricted fetal sheep increases circulating fetal insulin-like growth factor-I levels but not fetal growth

“…Cortisol has been shown to be a powerful stimulator of IGFBP-1 in humans independent of insulin and glucose (Conover et al 1993). Both postnatally (Lewitt & Baxter 1990, Nygren et al 1997 and prenatally (Gallaher et al 1992), glucose and insulin are thought to be the main regulators of IGFBP-1. In our study, fetal blood glucose levels were not significantly altered during the embolisation period, and are therefore unlikely to be the main regulator of IGFBP-1 in this scenario.…”