Activational Effects of Gonadal Steroids on Hypothalamo-Pituitary-Adrenal Regulation in the Rat Disclosed by Response to Dexamethasone Suppression

Previous studies demonstrated that gonadal steroids secreted during perinatal life permanently ‘organize’ the mechanisms governing hypothalamo‐pituitary‐adrenal (HPA) function, leading to sexually differentiated patterns of pituitary‐adrenal activity under basal and stress conditions. In this paper, we show that gonadal steroids can also exert ‘activational’ effects upon the HPA system. Examination of the ability of different doses of dexamethasone to suppress the nocturnal increase in corticosterone secretion and to attenuate the gene expression of CRH in the hypothalamic paraventricular nucleus of intact and gonadectomized male and female rats revealed that ovarian steroids make an important contribution to the higher sensitivity of the pituitary‐adrenal axis in females to glucocorticoid suppression, whereas testicular steroids may be causal to the male’s moderate responsiveness to glucocorticoid feedback. These findings may be implicated in a number of psychiatric and neurological disease states commonly associated with impaired HPA regulation, but which may be primarily rooted in altered gonadal steroid secretion.