Developmental regulation of glucogenesis in the sheep fetus during late gestation

1. Using tracer methodology, endogenous glucose production was measured in twenty-six chronically catheterized sheep fetuses during normal fed conditions and in response to a 48 h period of maternal fasting at different gestational ages during the last 10-15 days of gestation (term, 145 +/- 2 days). 2. In normal fed conditions, the rate of fetal glucose production was negligible until 143-145 days when it rose significantly to account for 50 % of the glucose used by the fetus. The rise in fetal glucogenesis towards term closely parallelled the normal prepartum rise in fetal plasma cortisol and catecholamines. 3. Maternal fasting for 48 h induced endogenous glucose production in fetuses at 139-141 days but not at 133-135 days of gestation. Maternal fasting also induced increases in the plasma cortisol and noradrenaline levels in all the fetuses studied. Fetal plasma cortisol levels at the end of the fast and the increment in fetal plasma cortisol during maternal fasting were significantly greater in the older groups of fasted animals. 4. When the data from all the fetuses were combined, partial correlation analysis of fetal glucose production and the log plasma concentrations of cortisol and total catecholamines showed that plasma cortisol was the predominant regulator of fetal glucogenesis during late gestation. However, once plasma cortisol levels exceeded 17.5 ng ml-1, plasma catecholamines were a major influence on fetal glucogenesis. 5. The results show that glucogenesis occurs in fetal sheep during late gestation in conditions in which the fetal plasma concentrations of cortisol and catecholamines are elevated. They also suggest that cortisol enhances the capacity for glucogenesis in utero, while catecholamines actually activate glucose production in sheep fetuses close to term.