Paradoxical effect of corticosteroids on pituitary ACTH/beta-endorphin release in stressed animals.

We have previously demonstrated a number of changes in the anterior lobe proopiomelanocortin (POMC) system in chronically stressed rats. The purpose of the present experiments was to investigate whether chronically stressed rats demonstrate changes in pituitary sensitivity to glucocorticoid negative feedback. To study this question we compared the effects of glucocorticoids on ovine corticotropin releasing factor (oCRF)-stimulated ACTH and beta-endorphin release from cell suspensions prepared from naive unhandled rats versus chronically stressed rats. After dexamethasone, there was a 50% decrease in oCRF-stimulated hormone release in control rats but no inhibition of oCRF-stimulated hormone release in anterior lobe suspension from chronically stressed rats. Rather, the chronically stressed group exhibited a 50% hormone increase above the oCRF-stimulated baseline. The same pattern was observed after the addition of corticosterone to the medium. These findings suggest that there may be a positive feedback effect of glucocorticoids at the pituitary level under some conditions of chronic stress.