Dexamethasone Suppresses ACTH Release Without Attenuating Pituitary Cyclic AMP Response to Stress in Vivo

Dexamethasone, a synthetic glucocorticoid, has been shown to decrease basal and stress-elevated levels of the pituitary hormone ACTH. Glucocorticoids are known to bind to multiple sites within the brain and pituitary and it not know which sites is most important in mediating the observed inhibition of ACTH release. At the level of the corticotroph, there is contradictory data from in vitro studies regarding whether dexamethasone acts proximal or distal to the formation of the cyclic AMP second messenger that has been shown to be involved in CRF stimulated ACTH release. In the present report, we have examined the effects of dexamethasone pretreatment on stress-induced elevations in pituitary cyclic AMP and the release of ACTH in vivo. Acute stress 15 min of intermittent footshock elevated levels of pituitary cyclic AMP and plasma plus 0.2 mgkg2 hr prior to sacrifice inhibited stress-induced elevations in plasma ACTH but did not affect pituitary cyclic AMP response to acute stress. These findings suggest that dexamethasone inhibits the release of ACTH via an action distal to the generation of cyclic AMP. Keywords Reprints Dexamethasone, Stress, ACTH, Rat, Pituitary, Cyclic AMP, Gluccocorticoid Biochemistry.