Maternal glucocorticoid treatment programs HPA regulation in adult offspring: sex-specific effects

Pregnant guinea pigs were treated with dexamethasone (1 mg/kg) or vehicle o n days 40-41, days 50-51, and days 60-61 of gestation. Adult offspring were split into two groups. Group 1 guinea pigs were catheterized, and the hypo thalamo-pituitary-adrenal (HPA) axis was tested in basal and activated stat es. Group 2 guinea pigs were euthanized with no further manipulation. In ma le offspring, prenatal dexamethasone exposure resulted in a significant red uction in brain-to-body weight ratio. Dexamethasone-exposed male offspring exhibited reduced basal and activated plasma cortisol levels, which was ass ociated with elevated hippocampal mineralocorticoid receptor (MR) mRNA and increased plasma testosterone. In females exposed to glucocorticoids in ute ro, basal and stimulated plasma cortisol levels were higher in the follicul ar and early luteal phases of the cycle, but this effect was reversed in th e late luteal phase, indicating a significant interaction of sex steroids. In female offspring (at estrus), glucocorticoid receptor mRNA levels were l ower in the paraventricular nucleus and pars distalis but higher in the hip pocampus in animals exposed to dexamethasone in utero. Hippocampal MR mRNA levels were significantly lower (similar to 50%) than in controls. In concl usion, repeated antenatal glucocorticoid treatment programs HPA function in a sex-specific manner, and these changes are associated with modification of corticosteroid receptor expression in the adult brain and pituitary.