Adrenal Glands Are Essential for Activation of Glucogenesis

31 In adults, the adrenal glands are essential for the metabolic response to stress but little is known 32 about their role in fetal metabolism. This study examined the effects of adrenalectomizing fetal 33 sheep on glucose and oxygen metabolism in utero in fed conditions and after maternal fasting for 34 48h near term. Fetal adrenalectomy (AX) had little effect on the rates of glucose and oxygen 35 metabolism by the fetus or uteroplacental tissues in fed conditions. Endogenous glucose 36 production was negligible in both AX and intact, sham operated fetuses in fed conditions. 37 Maternal fasting reduced fetal glucose levels and umbilical glucose uptake in both groups of 38 fetuses to a similar extent but activated glucose production only in the intact fetuses. The lack of 39 fasting-induced glucogenesis in AX fetuses was accompanied by falls in fetal glucose ultilization 40 and oxygen consumption not seen in intact controls. The circulating concentrations of cortisol 41 and total catecholamines, and the hepatic glycogen content and activities of key gluconeogenic 42 enzymes were also less in AX than intact fetuses in fasted animals. Insulin concentrations were 43 also lower in AX than intact fetuses in both nutritional states. Maternal glucose utilization and its 44 distribution between the fetal, uteroplacental and non-uterine maternal tissues were unaffected by 45 fetal adrenalectomy in both nutritional states. Ovine fetal adrenal glands, therefore, have little 46 effect on basal rates of fetal glucose and oxygen metabolism but are essential for activating fetal 47 glucogenesis in response to maternal fasting. They may also be involved in regulating insulin 48 sensitivity in utero. 49