PC41 EFFECT OF PARITY AND MATERNAL NUTRITION ON GH-IGF-I AXIS AND GLUCOCORTICOID RECEPTOR IN THE OVINE LIVER DURING POSTNATAL DEVELOPMENT

Abstract

Introduction: Sub-optimal maternal nutrition during pregnancy can effect offspring liver development as a consequence of changes in plasma GH, IGF-I mRNA and glucocorticoid receptor (GR) levels. Maternal parity has a significant impact on fetal growth but the extent to which it may affect neonatal GH receptor (GHR) and IGF-I mRNA and postnatal sensitivity to cortisol in the liver after birth is not known. Methods: Twenty-two twin bearing ewes of similar body weight were entered into the study of which 12 were primiparous (P) and 10 multiparous (M). Half of the ewes from each parity group were nutrient restricted (NR), consuming only 50% of total metabolisable energy requirements for the final month of gestation whilst the remainder were fed to requirements (C). At one day of age, one randomly selected lamb from each ewe was weighed and humanely euthanased. The remaining lamb was reared by its ewe until one month of age when tissue sampling was performed. The relative abundance of hepatic GHR, IGF-I and GR to 18S rRNA was measured by RT-PCR. Results are given as means and SEM in arbitrary units (a.u.) and expressed a percentage of a reference sample. Significant differences were analysed using independent t-tests (P<0.05). Results: Maternal parity had no effect on birth or body weight. Irrespective of maternal nutrition P offspring had smaller livers (birth: PC 85.5±8; MC 110.4±17 g (P=0.01); 1 month: PC 251±44.5; MC 419.2±20.1 g (P<0.01)). At birth, GHR mRNA abundance was increased in P offspring (PC 84 ±22; MC 21 ±7 a.u. (P<0.01)), whilst IGF-I mRNA expression was reduced (PC 102 ±3; MC 169 ±31 a.u.). These differences were unaffected by maternal nutrition. Conversely, hepatic GR mRNA was significantly raised by NR in M but not P offspring (MC: 114±12; MNR: 141±18 a.u (P<0.05)). By one month a significant decrease in GR was observed in all groups with the exception of PNR offspring (MNR: 64±3; PNR: 98±10 a.u (P<0.05)). Conclusion: Maternal parity is a major factor determining hepatic growth that is largely independent of maternal diet. At birth, P offspring have increased GHR/IGF-I ratios. At one month of age these offspring exhibit altered glucocorticoid sensitivity. The maintenance of higher GR in the livers of mothers who were both P and NR may be predicted to increase their sensitivity to environmental and metabolic stress in later life.