Effects of intravenous insulin-like growth factor-I and insulin administration on insulin-like growth factor-binding proteins in the ovine fetus

The insulin-like growth factors (IGF) are important anabolic hormones in th e mammalian fetus; their anabolic actions are potentially modulated by alte rations in the IGF-binding proteins (IGFBP). We have previously shown that the nutritional state of the fetus affects both IGF-l and the IGFBP concent rations. The present study was designed to determine the effect of alterati on,.; in insulin and IGF-l circulating concentrations on the IGFBPs. Becaus e both insulin and IGF-I elicit decreases in glucose and amino acid concent rations, the concentrations of these substrates were clamped during the hor mone infusions. Sixteen ovine fetuses were chronically catheterized at approximately 115 da ys of gestation, and experimental procedures performed at approximately 130 days of gestation. Insulin, IGF-I or both were infused for an 8-h period. Baseline concentrations of hormones and binding proteins were obtained, and concentrations were also obtained at the end of the infusion. Hepatic IGFB P-1 mRNA expression was also determined, Intravenous infusion of IGF-I sign ificantly increased IGF-1 concentrations in plasma in the ovine fetus. Intravenous infusion of insulin inhibited hepatic IGFBP-1 gene expression w hen amino acids and glucose were clamped. In contrast, intravenous infusion of recombinant human lGF-I (rhlGF-I) enhanced hepatic IGFBP-1 gene express ion. Neither insulin nor rhIGF-I treatment had an effect on hepatic IGFBP-3 gene expression. Insulin did not alter plasma IGFBP-1 significantly, but i t increased IGFBP-3 in plasma. rhIGF-I increased both IGFBP-1 and IGFBP-3 p rotein levels in plasma. The responses of IGFBP-1 and IGFBP-3 to increased plasma IGF-I and insulin may serve to protect the fetus from exaggerated anabolic effects and to blu nt the hypoglycemic potential of circulating IGFs and insulin.