THE EFFECT OF GLUCAGON ON PREGNANCY IN THE RAT

Pregnant Sprague–Dawley rats were given glucagon during the first, second, or third week of gestation. The effects on maternal and fetal physiology were studied and were compared with those of adrenaline. At all dose levels (0.5–2.0 mg/kg twice daily), glucagon significantly reduced maternal and fetal weights when given from day 13 to day 20 of gestation. Placenta weights were reduced, and there was a high incidence of premature and postmature deliveries, the latter associated with a high stillbirth rate. Glucagon (1.0 mg/kg twice daily) had little or no effect on maternal nitrogen balance or on fetal weight when given from day 0 to day 7 or from day 7 to day 13 of gestation. When administered from day 13 to day 20 there was a significant reduction in fetal weight compared with that of the controls, pair fed or fed ad libitum. Less nitrogen and probably more water were retained than in the controls. No significant increase in resting oxygen consumption was detected after injection of glucagon. The results indicate that the effect of excess glucagon on the fetus is mediated partly by a reduction in maternal food intake and partly by increased maternal protein catabolism. It seems unlikely to be due to an increase in resting expenditure of maternal energy or to the liberation of endogenous adrenaline. The increase in glucagon sensitivity in late pregnancy may be related to an increase in insulin resistance, known to occur at this time.