EFFECT OF INSULIN ON HUMAN CHORIONIC-GONADOTROPIN SECRETION BY PLACENTAL EXPLANTS

The effect of physiological concentrations of insulin (5 - 50 muU/ml) was tested on human chorionic gonadotrophin (HCG) secretion by first trimester (7-9 weeks) and term placental explants using both static and dynamic culture models. In static cultures, insulin exerted a significant biphasic inhibitory effect (80% at 5 muU/ml and 40% at 50 muU/ml) on HCG secretion by placental explants. At approximate fasting plasma levels, 25 muU/ml insulin added to superfused explants for greater-than-or-equal-to 8 min also had a rapid inhibitory effect. A delayed inhibitory effect on HCG pulsatility was also observed using 25 muU/ml insulin, with a 2-fold decrease in HCG pulse amplitude and a 4-fold decrease in the area under the curve following overnight pre-incubation (P < 0.01). Insulin had no effect in static cultures at term. The effect of insulin-like growth factor (IGF-I) and fibroblast growth factor (bFGF) on HCG secretion in static cultures was not statistically significant. In conclusion, physiological concentrations of insulin inhibit HCG secretion in first trimester placenta in vitro. This effect is gestational age dependent and specific since it is not mimicked by IGF-I or bFGF. Thus, insulin may be an important modulator of trophoblastic HCG secretion during early pregnancy.