Early growth retardation induced by excessive exposure to glucocorticoids in utero selectively increases cardiac GLUT1 protein expression and Akt/protein kinase B activity in adulthood

In the rat, dexamethasone treatment during late pregnancy leads to intraute rine growth retardation and is used as a model of early programming of adul t onset disease. The present study investigated whether pre-natal dexametha sone treatment modifies cardiac glucose transporter (GLUT) protein expressi on in adulthood and identified signalling pathways involved in the response . Dexamethasone (100 mug/kg body wt per day) administered via an osmotic pu mp to pregnant rats (day 15 to day 21; term=22 to 23 days) reduced fetal we ight at day 21 and caused hypertension, hyperinsulinaemia and elevated cort icosterone levels ill the adult (21-week-old) male offspring. Cardiac GLUT1 protein expression was selectively up-regulated (2.5-fold; P<0.001), in th e absence of altered cardiac GLUT4 protein expression, in adult male offspr ing of dexamethasone-treated dams. Maternal dexamethasone treatment did not influence cardiac GLUT1 protein expression during fetal or early post-nata l life. We examined potential regulatory signalling proteins that might med iate up-regulation of cardiac GLUT1 protein expression in adulthood. We obs erved marked (2.2-fold; P<0.01) activation of Akt/protein kinase B (PKB), t ogether with modest activation of the anti-apoptotic protein kinase C (PKC) isoforms PKC a (88%, P<0.05) and PKC <epsilon> (56%, P<0.05) in hearts of the early-growth-retarded male offspring. These effects were, however, obse rved in conjunction with up-regulation of cardiac protein expression of PKC <beta>(1) (191%, P<0.01), PKC <beta>(2) (49%, P<0.05) and PKC <delta> (35% ; P<0.01), effects that may have adverse consequences. Maternal dexamethaso ne treatment was without effect on cardiac extracellular signal-related kin ase (ERK) 1 or ERK2 activity in adulthood. In conclusion, our data demonstr ate an effect of maternal dexamethasone treatment to up-regulate cardiac GL UT1 protein expression in early-growth-retarded, hypertensive, hyperinsulin aemic adult male offspring, an effect observed in conjunction with activati on of Akt/PKB.