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Received March 2, 2004
Revised March 30, 2004
Accepted after revision May 12, 2004
1 University of Toronto
* To whom correspondence should be addressed. E-mail: stephen.matthews{at}utoronto.ca.
Pregnant guinea pigs were treated with dexamethasone (1 mg/kg) or vehicle on days 40-41, 50-51 and 60-61 of gestation, after which animals delivered normally. Adult male offspring were catheterized at 145 days of age and subjected to tests of HPA axis function in basal and activated states. Animals exposed to dexamethasone in utero (mat-dex) exhibited increased hippocampus to brain weight ratio, increased adrenal to body weight ratio and increased mean arterial pressure. There were no effects on gestation length, birth weight and postnatal growth. There were no overall differences in diurnal plasma ACTH and cortisol profiles, though there were subtle differences during the subjective afternoon between control and mat-dex offspring. A significant decrease in initial ACTH suppression was observed following dexamethasone injection in mat-dex offspring compared to control offspring. Molecular analysis revealed significantly increased MR mRNA expression in the limbic system and particularly in the dentate gyrus in mat-dex offspring. In the anterior pituitary, both POMC and GR mRNA levels were significantly elevated in mat-dex offspring. In conclusion, 1) repeated prenatal treatment with synthetic glucocorticoid (sGC) permanently programs organ growth, blood pressure and HPA regulation in mature male offspring and these changes involve modification of corticosteroid receptor expression in the brain and pituitary; 2) Effects of prenatal sGC exposure on HPA function appear to change as a function of age, indicating the importance of investigating HPA and cardiovascular outcome at multiple time points throughout life.
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