Programming hyperglycaemia in the rat through prenatal exposure to glucocorticoids - fetal effect or maternal influence?

In a previous study, we showed that exposure of rats to dexamethasone (Dex) selectively in late pregnancy produces perrrianent induction of hepatic ph osphoenolpyruvate carboxykinase (PEPCK) expression and hyperglycaemia in th e adult offspring. The mechanisms by which glucocorticoids cause this progr amming are unclear but may involve direct actions on the fetus/neonate, or glucocorticoids may act indirectly by affecting maternal postnatal nursing behaviour. Using a cross-fostering paradigm, the present data demonstrate t hat switching the offspring at birth from Dex-treated dams to control dams does not prevent induction of PEPCK or hyperglycaemia. Similarly, offspring born to control dams but reared by Dex-treated dams from birth maintain no rmal glycaemic control. During the neonatal period, injection of saline per se was sufficient to cause exaggeration in adult offspring responses to an oral glucose load, with no additional effect from Dex. However, postnatal treatment with either saline or Dex did not alter hepatic PEPCK activity. P renatal Dex permanently raised basal plasma corticosterone levels, but unde r stress conditions there were no differences in circulating corticosterone levels. Likewise, Dex-exposed rats had similar plasma catecholamine concen trations to control animals. These findings show that glucocorticoids progr amme hyperglycaemia through mechanisms that operate on the fetus or directl y on the neonate, rather than via effects that alter maternal postnatal beh aviour during the suckling period. The hyperglycaemic response does not app ear to result from abnormal sympathoadrenal activity or hypothalamic-pituit ary-adrenal response during stress.