Insulin-like growth factor 1 (IGF-1) is an anabolic hormone in postnatal life and may be an important endocrine regulator of fetal growth. However, its effects on fetal metabolism in vivo have not previously been determined. We studied the effect of 50 micrograms/h.kg IGF-1 infusion in 12 chronically catheterized fetal sheep. Fetal blood amino nitrogen concentrations fell 10% and maternal 7%, consistent with a rise in feto-placental amino acid uptake. Fetal amino acid oxidation, measured by fetal urea production fell by 30% (44.4 +/- 10.5 to 30.9 +/- 8.0 mumol/min). Fetal and maternal blood glucose concentrations both fell by 0.1 mM, consistent with increased feto-placental glucose uptake. Placental lactate production fell 30% (114 +/- 15 to 78 +/- 11 mumol/min), as did fetal and uterine lactate uptake. There was no change in umbilical or uterine blood flows, nor in placental transfer by simple or facilitated diffusion. We conclude that IGF-1 has anabolic effects on feto-placental protein and carbohydrate metabolism. Circulating IGF-1 may in part mediate the regulation of fetal growth in response to fetal nutrient supply.

Insulin-like growth factor-I (IGF-I) in the maternal circulation may have a role in the regulation of placental function and fetal growth, but its mechanisms of action are not known. We studied the effects of maternal IGF-I infusion (30 micrograms/kg.h for 4 h) in eight chronically catheterized pregnant sheep. IGF-I infusion caused an increase in fetal blood glucose concentrations, but no change in placental or fetal glucose uptake. Maternal plasma insulin concentrations fell. Placental lactate production increased by 56%, with most of this lactate taken up by the fetus. Maternal and fetal blood amino nitrogen concentrations fell, but fetal protein oxidation was unchanged. IGF-I infusion did not change feto-placental oxygenation, placental blood flow, or placental transfer by simple or facilitated diffusion. The metabolic effects of maternal IGF-I infusion in part oppose those of fetal IGF-I. We hypothesize that the balance of maternal and fetal IGF-I concentrations contributes to the regulation of substrate distribution between mother, placenta and fetus, and may thus mediate the nutritional regulation of fetal growth.