Differential changes in insulin-like growth factors and their binding proteins following asphyxia in the preterm fetal sheep

1. The purpose of this study was to examine the changes in circulating conc entrations of insulin-like growth factor (IGF)-I, IUF-II, IGF-binding prote in (IGFBP)-1, IGFBP-2 and insulin following asphyxia in utero. 2. Fetal sheep at 90-93 days gestation underwent either sham occlusion (n = 7) or asphyxia (n = 6) induced by complete umbilical cord occlusion for 30 min. Fetal blood samples were taken before occlusion and 4, 6, 24, 48 and 72 h post-occlusion. 3. During the early phase of recovery there was a substantial fall (80%) in circulating plasma IGF-I concentrations by 6 h post-asphyxia (P<0.001). Th is was associated with a rapid rise in IGFBP-1 (P < 0.001), but no change i n IGF-II or IGFBP-2. Insulin was significantly reduced at 4 h (P < 0.001) a nd glucose slightly elevated (P < 0.05), but insulin values returned to bas eline by 6 h. Between 24 and 72 h of recovery, IGF-I gradually increased, I GFBP-1 returned to control values, and there was an increase in IGFBP-2 aft er 24 h (P< 0.05) and IGF-II by 72 h (P < 0.05) after asphyxia. 4. These data demonstrate a differential effect uf asphyxia on the IGF asis of the premature fetal sheep. A key finding was the large fall in circulat ing IGF-I, but not IGF-II, during the early phase of recovery. IGF-I bioava ilability was, in part, regulated by IGFBP-1, but maximal changes in IGF-I and IGFBP-1 were independent of plasma insulin and glucose. 5. The impact of this substantial change in circulating IGF-I on the fetus is unknown. It may facilitate metabolic requirements by promoting cababolis m. Alternatively, as IGFs play a role in wound repair, the acute changes in IGF-I and IGFBP-1 may reflect transport of IGF from the circulatory pool t o injured tissues to promote wound repair.