SEX-SPECIFIC EFFECTS OF PRENATAL STRESS ON HYPOTHALAMIC-PITUITARY-ADRENAL RESPONSES TO STRESS AND BRAIN GLUCOCORTICOID RECEPTOR DENSITY IN ADULT-RATS

Previous research indicates that the offspring of dams exposed to stre ss during late gestation show altered hypothalamic-pituitary-adrenal ( HPA) responses to stress. However, the results are inconsistent and a review of the literature suggests that the effects may differ dependin g upon the gender of the offspring. In the present study, we measured plasma adrenocorticotropin (ACTH) and corticosterone (B) levels prior to, and at 0, 20, 40 and 70 min following restraint stress in catheter ized adult male and female offspring of dams stressed in the last week of gestation (i.e. days 15-19 of gestation). Prenatal stress signific antly increased both plasma ACTH and B levels in response to restraint , but only in females; male offspring were largely unaffected. In addi tion, plasma corticosteroid-binding globulin (CBG) levels were signifi cantly increased in prenatally-stressed females, but not in males. Des pite these differences in plasma CBG, estimated free B levels followin g restraint were also significantly elevated in prenatally-stressed fe males. We then examined glucocorticoid receptor binding in a variety o f forebrain structures. Prenatal stress had no effect on glucocorticoi d receptor density in the hypothalamus or hippocampus in either males or females. Differences in glucocorticoid receptor density across grou ps were observed in the septum, frontal cortex, and amygdala. However, the pattern of observed differences across the groups was not consist ent with the pattern of hormonal differences. In summary, the effect o f prenatal stress on HPA function is substantially more marked in fema les than in males. Interestingly, a similar pattern of effects on HPA activity has been reported for prenatal alcohol exposure.