Effects of glucose on placental hormones in the human term placenta in vitro

Glucose intake during pregnancy results in a decrease in endogenous insulin-like growth factor binding protein-1 (IGFBP-1). However, the exact role of glucose on placental secretion of IGFBP-1 is unclear. This study was designed to investigate the direct effects of glucose on the production of IGFBP-1 and other placental hormones, using an isolated placental preparation. Using the dual recirculating perfusion system for an isolated human placenta lobule, a total of 43 experiments were performed over a duration of 6 hours. Twenty placentae were perfused with a medium containing 141 ± 10 mg/dL (7.83 ± 0.56 mmol/L) glucose (group I) and 23 placentae with 242 ± 12 mg/dL (13.43 ± 0.67 mmol/L) glucose (group II). Levels of insulin, glucose, lactate, insulin-like growth factor (IGF-I), IGFBP-1, human placental lactogen (hPL) and β-human chorionic gonadotropin (β-hCG) were measured at 30 minute intervals during perfusion. Insulin and IGF-1 were barely detectable in the perfusates and their levels were not modulated by glucose. IGFBP-I was predominantly detected in the maternal rather than the fetal compartment of the placental circulation. Glucose increased the levels of IGFBP-1 in the maternal circulation in groups I and II during the first two hours of perfusion (188 ± 58% and 193 ± 31%, respectively). However, during the subsequent 4 hour period, the increase in IGFBP-1 concentration was significantly higher in group II (926 ± 427%) than in group I (428 ± 216%) (p < 0.05). There was no difference in the levels of hPL or β-hCG between the two groups in the maternal circulation. Thus, glucose stimulates the production of IGFBP-1 in the maternal circulation of a placenta in vitro. This increase in IGFBP-1 by glucose in vitro, as opposed to the decrease of IGFBP-1 in vivo, may be due to a lack of circulatory maternal insulin in the isolated placental preparation. These results also suggest that there may be a functional barrier within the placenta that prevents an increase in the level of IGFBP-1 in the fetal circulation.