Localisation and expression of insulin-like growth factor I receptor protein in human placental syncytiotrophoblast

Abstract

The human fetus requires more glycine than any other amino acid but placental glycine transfer to the fetus is insufficient to meet fetal demand. l-Serine could represent a major metabolic source of glycine for the human fetus but little is known about the kinetics and physiology of l-serine uptake by the human placenta. We have characterised the amino acid transport systems involved in the uptake of l-serine by the microvillous membrane of the human placental syncytiotrophoblast and compared the uptake rates to those of glycine.l-Serine uptake into microvillous membrane (MVM) vesicles was primarily mediated by system A (MeAIB inhibitable) and system L (BCH inhibitable). Further characterisation using specific substrates of LAT1 and LAT2 found the pattern of l-serine uptake was consistent with that expected for uptake mediated by LAT2. Uptakes were performed with tracer levels of 14C-l-serine, physiological levels of l-serine, or with physiological levels of amino acids. As amino acid concentrations rose, the proportion of uptake by System L decreased while uptake by uncharacterised Na+-independent systems increased.Uptake of l-serine into MVM vesicles had a Vmax of 2.1 ± 0.4 nmol/mg protein/min, which was significantly higher than for glycine (Vmax 1.0 ± 0.2 nmol/mg protein/min). This indicates that MVM vesicles have a higher uptake capacity for l-serine than glycine, despite a greater demand for glycine over serine for fetal protein synthesis. Further studies are now required to define the fate of l-serine taken up by the placenta and its importance for the fetus.