Restriction of placental growth in sheep enhances placental metabolism of fetal β-endorphin-like immunoreactivity

The opioid polypeptide β-endorphin is present in fetal blood but it is not clear whether its source is the fetus or the placenta. We therefore measured β-endorphin in extracts of fetal femoral arterial and umbilical venous blood plasma in sheep by radioimmunoassay to determine whether the fetus or the placenta is the major source of β-endorphin in the fetal circulation. Chromatographic analysis of extracts of fetal arterial plasma showed that β-lipotropin and other precursors of β-endorphin made only a minor contribution to the immunoreactivity detected. Concentrations of immunoreactive β-endorphin were higher in the femoral artery than in the umbilical vein in fetal sheep between 113 and 128 days of pregnancy. Therefore the placenta removes β-endorphin or a closely related polypeptide of fetal origin from the umbilical circulation in sheep at this stage of gestation. Acute hypoxaemia and hypoglycaemia increase the concentrations of immunoassayable β-endorphin in blood plasma of adult and fetal sheep, but little is known about the effects of chronic hypoxaemia or hypoglycaemia on the circulating levels of β-endorphin and related polypeptides in the fetus. Therefore we also measured immunoreactive β-endorphin in blood plasma from fetal sheep in which growth retardation in association with restricted placental growth was produced by removal of endometrial caruncles before mating. Intra-urterine growth retardation was accompanied by chronic hypoglycaemia and chronic hypoxaemia in the fetuses. This was not associated with higher concentrations of β-endorphin-like immunoreactivity in fetal arterial or umbilical venous plasma, but was accompanied by significantly increased placental extraction of fetal immunoreactive β-endorphin from the umbilical circulation. The study shows that the fetus is the source and the placenta is a major site of clearance of immunoreactive β-endorphin from the fetal circulation in sheep, that circulating concentrations of β-endorphin-related peptides in fetal sheep are not significantly elevated in association with fetal growth retardation, and suggests that increased placental clearance of β-endorphin or a closely related peptide may maintain concentrations of immunoreactive β-endorphin in fetal blood near normal levels during intra-uterine growth retardation, in cannulated fetal sheep between 113 and 128 days of gestation.