Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2009) 19 P111

SFEBES2009 Poster Presentations Cytokines and growth factors (6 abstracts)

Glucose does not influence placental regulation of insulin-like growth factor bioavailability during pregnancy

Alexandra Lubina Solomon , Philip N Baker , J Martin Gibson , John D Aplin & Melissa Westwood


University of Manchester, Manchester, UK.


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.

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