Gender, Sex Steroids, Corticotropin-Releasing Factor, Nitric Oxide, and the HPA Response to Stress

Abstract

We used two stresses—exposure to mild electrofoot shocks (a neurogenic stress) and acute alcohol injection (a systemic stress)—to investigate the influence of gender and circulating sex steroids on ACTH and corticosterone released by adult rats. Both types of stresses significantly increased plasma levels of these hormones. Following exposure to shocks, intact females secreted significantly more ACTH than intact males, a difference that was abolished by ovariectomy. Gender differences in corticosterone responses were sometimes, but not always, present. In contrast, in this series of experiments males released more ACTH when acutely injected with alcohol, while there was no obvious effect of sex on corticosterone secretion. Corticotropin-releasing factor (CRF) antagonists were more effective at reducing ACTH compared to corticosterone levels. Finally, pituitary response to CRF, but much less so to vasopressin (VP), was larger in intact females compared to intact males. Blockade of endogenous nitric oxide formation slightly enhanced the effect of CRF in males, but not in females, and while it produced the expected enhancement of VP-induced ACTH release, this effect was more pronounced in females. Collectively, these results provide evidence for an influence of circulating sex steroids on pituitary and adrenal activity under some, but not all circumstances.