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 concentrations of insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein (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). This was associated with a rapid rise in IGFBP-1 (P < 0.001), but no change in IGF-II or IGFBP-2. Insulin was significantly reduced at 4 h (P < 0.001) and glucose slightly elevated (P < 0.05), but insulin values returned to baseline by 6 h. Between 24 and 72 h of recovery, IGF-I gradually increased, IGFBP-1 returned to control values, and there was an increase in IGFBP-2 after 24 h (P < 0.05) and in IGF-II by 72 h (P < 0.05) after asphyxia. 4. These data demonstrate a differential effect of asphyxia on the IGF axis of the premature fetal sheep. A key finding was the large fall in circulating IGF-I, but not IGF-II, during the early phase of recovery. IGF-I bioavailability 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 catabolism. Alternatively, as IGFs play a role in wound repair, the acute changes in IGF-I and IGFBP-1 may reflect transport of IGF-I from the circulatory pool to injured tissues to promote wound repair.
Research Centre for Developmental Medicine and Biology, Department of Paediatrics, The University of Auckland, Auckland, New Zealand. l.bennett@auckland.ac.nz
L
L
Bennet
M H
MH
Oliver
A J
AJ
Gunn
M
M
Hennies
B H
BH
Breier
D000818:Animals; D001237:Asphyxia / Q000097:blood*; D005312:Fetal Blood / Q000378:metabolism; D005315:Fetal Diseases / Q000097:blood*; D005865:Gestational Age; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D012756:Sheep; D013002:Somatomedins / Q000032:analysis*
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II