Effects of repeated antenatal dexamethasone (dex) exposure on hypothalamic-pituitary-adrenal (HPA) function in mature adult guinea pigs (Cavis porcellus).

摘要

We examined the effects of antenatal glucocorticoid treatment on mature adult hypothalamic-pituitary-adrenal (HPA) function in guinea pigs. Pregnant guinea pigs were treated with dexamethasone or vehicle on days 40/41, 50/51 and 60/61 of gestation, after which animals delivered normally. Offspring were catheterized at 145 days of age and subjected to tests of HPA axis function. Male offspring exposed to dexamethasone in utero exhibited decreased basal cortisol, increased HPA sensitivity to challenge, increased hippocampus to brain weight ratio, increased adrenal to body weight ratio and increased mean arterial pressure. Female offspring born to dex-treated mothers showed a significant increase in basal cortisol during the low progesterone phase and an increase in HPA sensitivity irrespective of progesterone. Changes in endocrine data were consistent with changes in mineralocorticoid receptor in the limbic system and glucocorticoid receptor in the pituitary. In conclusion, repeated antenatal glucocorticoid exposure permanently modifies offspring HPA function in sex-specific manner.