Endocrine Abstracts

Abnormal fetal growth remains a problem in pregnancies, complicated by diabetes and is associated with increased maternal and offspring mortality and morbidity. Insulin-like growth factors (IGFs) are important regulators of fetal growth. Their effects are controlled by binding proteins (IGFBPs). IGFBP-1 is particularly important in pregnancy. Phosphorylated IGFBP-1 (pIGFBP-1) has a high affinity for IGF-I and inhibits IGF-I actions, whereas de-phosphhorylated IGFBP-1 has a lower affinity for IGF-I and enhances its effect. We hypothesised that IGFBP-1 de-phosphorylation occurs in placenta and the process is catalysed by placental alkaline phosphatase (PLAP) and further speculated that diabetic macrosomia may be a consequence of elevated IGF action at the placenta.

We have established a model for pregnancy, complicated by diabetes by culturing term placentas from normal human pregnancies in variable glucose concentrations (5–25 mmol/l). These placentas or their conditioned media (CM) were incubated with pIGFBP-1. The effect on IGFBP-1 phosphorylation status was assessed by n-octyl glucoside gel electrophoresis and western/ligand blotting.

Results: Placental explants and their CM were shown to contain PLAP. pIGFBP-1 was de-phosphorylated following incubation with placenta, but not placental-CM. IGFBP-1 was found to bind the tissue, and it appears this binding is necessary for optimal de-phosphorylation. Culturing placenta in different glucose conditions did not alter PLAP expression and had no impact on the ability of placenta to de-phosphorylate IGFBP-1.

Conclusions: Placenta de-phosphorylates IGFBP-1, most probably as a result of PLAP activity. In vitro PLAP was not altered by acute exposure to high glucose. Further work is required to reveal mechanisms by which the maternal/ placental IGF-IGFBP-PLAP system modulates fetal growth in normal gestation and in pregnancy, complicated by diabetes.