Reversal of the hypothalamo-pituitary-adrenal response to oestrogens around puberty

The neuroendocrine gender dimorphism that begins during perinatal development is completed during puberty. We have previously described how the perinatal gonadal steroids programme hypothalamic–pituitary–adrenal (HPA) activity in adulthood and we now assess the role of peripubertal ovarian hormones. Prepubertal females were treated subcutaneously with either cholesterol or 17β-oestradiol and their pituitary–adrenal activity was assessed 5 days later. Oestradiol suppressed the ACTH and corticosterone responses to restraint stress in the prepubertal female. Furthermore, groups of female rats were ovariectomised (OVX) either before or after puberty and adult animals were subsequently treated with subcutaneous implants containing either 17β-oestradiol or cholesterol. Corticosterone pulsatility was assessed using an automated blood sampling system to collect blood from freely moving animals at 10 min intervals over 24 h. Oestradiol administered to adults that had been OVX either pre- or post-pubertally displayed a significantly higher mean corticosterone level as well as increased pulse frequency and pulse amplitude compared with cholesterol treated controls. These data demonstrate a reversal in the effect of oestrogens on HPA axis activity over the time of puberty with inhibitory effects prepubertally and stimulatory actions after puberty and imply an ovarian steroid-independent mechanism of pubertal maturation of HPA sensitivity to oestrogens.