Chronic pulsatile infusion of growth hormone to growth-restricted fetal sheep increases circulating fetal insulin-like growth factor-I levels but not fetal growth.

Abstract

Intra-uterine growth restriction (IUGR) is a major cause of perinatal mortality and morbidity. Postnatally, growth hormone (GH) increases growth, increases circulating insulin-like growth factor (IGF)-I levels, and alters metabolism. Our aim was to determine if GH infusion to IUGR fetal sheep would alter fetal growth and metabolism, and thus provide a potential intra-uterine treatment for the IUGR fetus. We studied three groups of fetuses: control, IUGR+ vehicle and IUGR+GH (n=5 all groups). IUGR was induced by repeated embolisation of the placental vascular bed between 110 and 116 days of gestation (term=145 days). GH (3.5 mg/kg/day) or vehicle was infused in a pulsatile manner from 117 to 127 days of gestation. Embolisation reduced fetal growth rate by 25% (P<0.01) and reduced the weight of the fetal liver (20%), kidney (23%) and thymus (31%; all P<0.05). GH treatment further reduced the weight of the fetal kidneys (32%) and small intestine (35%; both P<0.04), but restored the relative weight of the fetal thymus and liver (P<0.05). Embolisation decreased fetal plasma IGF-I concentrations (48%, P<0.001) and increased IGF binding protein 1 (IGFBP-1) concentrations (737%, P<0.002). GH treatment restored fetal plasma IGF-I concentrations to control levels, while levels in IUGR+vehicle fetuses stayed low (P<0.05 vs control). IGFBP-1 and IGFBP-2 concentrations were about sevenfold lower in amniotic fluid than in fetal plasma, but amniotic and plasma concentrations were closely correlated (r=0.75, P<0.0001 and r=0.55 P<0.0001 respectively). Embolisation transiently decreased fetal blood oxygen content (40%, P<0.002), and increased blood lactate concentrations (213%, P<0.04). Both returned to pre-embolisation levels after embolisation stopped, but blood glucose concentrations declined steadily in IUGR+vehicle fetuses. GH treatment maintained fetal blood glucose concentrations at control levels. Our study shows that GH infusion to the IUGR fetal sheep restores fetal IGF-I levels but does not improve fetal growth, and further reduces the fetal kidney and intestine weights. Thus, fetal GH therapy does not seem a promising treatment stratagem for the IUGR fetus.

• Authors: M K Bauer, B B Breier, F H Bloomfield, E C Jensen, P D Gluckman, J E Harding
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 177 Issue 1 Pg. 83-92 (Apr 2003) ISSN: 0022-0795 [Print] England
• PMID: 12697039 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin-Like Growth Factor Binding Protein 1
• Insulin-Like Growth Factor Binding Protein 2
• Insulin-Like Growth Factor I
• Insulin-Like Growth Factor II
• Growth Hormone

Topics

• Animals
• Embryonic and Fetal Development (drug effects)
• Female
• Fetal Blood (chemistry)
• Fetal Growth Retardation (drug therapy)
• Growth Hormone (therapeutic use)
• Infusions, Intravenous
• Insulin-Like Growth Factor Binding Protein 1 (blood)
• Insulin-Like Growth Factor Binding Protein 2 (blood)
• Insulin-Like Growth Factor I (analysis)
• Insulin-Like Growth Factor II (analysis)
• Models, Animal
• Placental Circulation
• Pregnancy
• Sheep
• Treatment Failure