Circulating insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs) and tissue mRNA levels of IGFBP-2 and IGFBP-4 in the ovine fetus

Abstract

The IGF-binding proteins (IGFBPs) are a family of at least six structurally related proteins, which bind the IGFs and modulate their actions, including the regulation of pre- and postnatal growth. In this study we have examined the relationship between circulating and tissue mRNA levels of IGFBPs and related this to circulating IGFs in the fetal sheep over the gestational period when rapid growth and development occurs. Circulating IGFBP-2, as measured by Western ligand blot (WLB), increases between early and mid gestation, remains high, then declines throughout late gestation (P = 0.0002). Circulating IGFBP-3 increases throughout gestation, as measured by WLB or RIA (P = 0.04 and P = 0.0001 respectively), as does circulating IGFBP-4 (P = 0.004). These ontogenic changes in circulating IGFBPs-2 and -4 are paralleled by changes in liver mRNA for these proteins and, for IGFBP-2, by those in kidney IGFBP-2 mRNA also. This suggests that liver and kidney may be the primary contributors to circulating IGFBP-2 and the liver to circulating IGFBP-4, IGFBP-2 mRNA is present in the heart and lung in early gestation but barely detectable in these tissues after approximately 60 days gestation. IGFBP-4 mRNA is also present in the heart in early but not late gestation, but is abundant in the lung throughout gestation. These results demonstrate tissue specific and developmental regulation of IGFBPs-2 and -4 at the mRNA level. To assess any role the circulating IGFs may play in mediating these changes in IGFBPs, or vice versa, both plasma IGF-I and IGF-II were measured by RIA. Circulating IGF-I increases as gestation progresses (P = 0.0001), while circulating IGF-II increases between early and mid gestation, remains high (P = 0.01), then declines. Circulating IGF-I is positively correlated with fetal weight (r = 0.66, P = 0.03), circulating IGFBP-3 (r = 0.54, P = 0.01) and IGFBP-4 (r = 0.52, P = 0.01). Circulating IGF-II positively correlates with circulating IGFBP-2 (r = 0.48, P = 0.02) throughout gestation and at 1 day postnatally. These relationships are consistent with circulating IGF-I influencing IGFBPs-3 and -4, and similarly, IGF-II determining IGFBP-2, or vice versa. Alternatively, these correlations may reflect coordinate regulation of IGF and IGFBP by a common factor.

Heifer nutrient intake during early- and mid-gestation programs adult offspring adiposity and mRNA expression of growth-related genes in adipose depots

“…Inter-assay coefficient of variation (CV) for HPLC separation and RIA of IGF1 in progeny plasma was 10.9% (nZ18 assays) and the intra-assay covariance for extraction and assay was 22.0% for a calf QC sample containing 31.4 ng/ml of IGF1. Total IGFBP concentrations were measured by analysis of neutralized fraction 1 in the same assay (Carr et al 1995). Progeny inter-assay CV was 9.7% (nZ9 assays) and intra-assay covariance for extraction and assay 21.6% for a calf QC sample containing 78.0 ng/ml of IGF2.…”

Insulin-like growth factor levels during pregnancy in the cow are affected by protein supplementation in the maternal diet

“…Both IGFs increase protein and glycogen synthesis in foetal tissues but it is thought that IGF I may have a more prominent role in modulating cell proliferation in specific endocrine and nutritional conditions in utero whereas IGF II provides a general stimulus for cell growth in utero and may also be responsible for developmental and tissue-specific changes in cell differentiation (Fowden, 1995). A strong positive correlation has been reported between IGF I levels in the foetus and foetal size in late gestation (Jones et al, 1988;Dwyer and Stickland, 1992a;Carr et al, 1995).…”

Effects of acute and chronic food restriction on the insulin-like growth factor axis in the guinea pig

“…Briefly, plasma was first acidified to pH 2·5 to dissociate IGFs from IGFBPs, and then delipidated, ultrafiltered and fractionated by size exclusion high performance liquid chromatography at pH 2·5 (Carr et al 1995). This procedure completely separated IGFBPs from IGFs in guinea pig plasma, as previously demonstrated with serum and plasma from pig (Owens et al 1990), sheep (Carr et al 1995) and human (Gargosky et al 1990). All of the IGF-I and IGF-II in guinea pig plasma was recovered in the chromatography effluent eluting between 8·75 min and 10·75 min after injection of diluted, acidified guinea pig plasma.…”