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K L Franko, A J Forhead and A L Fowden

Glucocorticoid administration during pregnancy programmes cardiovascular and metabolic functions in the adult offspring. Often, the control procedures are stressful per se and raise maternal glucocorticoid concentrations. This study compared the effects of maternal injection with dexamethasone (dex, 200 μg/kg) or saline with no treatment from 15 to 20 days of rat pregnancy on offspring growth and glucose metabolism. Near term, maternal corticosterone concentrations were higher in the saline-treated dams and lower in the dex-treated dams relative to untreated animals. In both male and female offspring, growth rate was measured for 14 weeks, and glucose tolerance was assessed between 12 and 13 weeks together with body fat content and plasma concentrations of insulin, leptin, and corticosterone between 14 and 15 weeks. Offspring liver was collected at different ages and was analyzed for glycogen content and gluconeogenic enzyme activity. Compared with untreated animals, both dex and saline treatments altered postnatal growth although adult body weight was unaffected. The two treatments had different effects on adult insulin concentrations and on hepatic glycogen content and gluconeogenic enzyme activities both pre- and postnatally. Relative to untreated animals, adult glucose tolerance was improved by maternal saline injection in males but not in females, while it was impaired in female offspring but not in male offspring of the dex-treated dams. Adult glucose tolerance was related to male body fat content but not to female body fat content. Dex and saline treatments of pregnant rats have differential sex-linked effects on the growth and glucose metabolism of their offspring, which indicates that the programming actions of natural and synthetic glucocorticoids may differ.

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K L Franko, D A Giussani, A J Forhead and A L Fowden

Fetal glucocorticoids have an important role in the pre-partum maturation of physiological systems essential for neonatal survival such as glucogenesis. Consequently, in clinical practice, synthetic glucocorticoids, like dexamethasone, are given routinely to pregnant women threatened with pre-term delivery to improve the viability of their infants. However, little is known about the effects of maternal dexamethasone treatment on the glucogenic capacity of either the fetus or mother. This study investigated the effects of dexamethasone treatment using a clinically relevant dose and regime on glycogen deposition and the activities of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) in the liver and kidney of pregnant ewes and their fetuses, and of non-pregnant ewes. Dexamethasone administration increased the glycogen content of both the fetal and adult liver within 36 h of beginning treatment. It also increased G6Pase activity in the liver and kidney of the fetuses but not of their mothers or the non-pregnant ewes. Neither hepatic nor renal PEPCK activity was affected by dexamethasone in any group of animals. These changes in glycogen content and G6Pase activity were accompanied by rises in the plasma glucose and insulin concentrations and by a fall in the plasma cortisol level in the fetus and both groups of adult animals. In addition, dexamethasone treatment raised fetal plasma tri-iodothyronine (T3) concentrations and reduced maternal levels of plasma T3 and thyroxine, but had no effect on thyroid hormone concentrations in the non-pregnant ewes. These findings show that maternal dexamethasone treatment increases the glucogenic capacity of both the mother and fetus and has major implications for glucose availability both before and after birth.