Fast Feedback Inhibition of the HPA Axis by Glucocorticoids Is Mediated by Endocannabinoid Signaling

• DOI: 10.1210/en.2010-0285
• Publication Date: 2010-08-12T02:02:16Z
• Authors: Nathan K. Evanson; Jeffrey G. Tasker; Matthew N. Hill; Cecilia J. Hillard; James P. Herman
• Keywords: Negative feedback; Corticosterone

Glucocorticoid hormones are secreted in response to stimuli that activate the hypothalamo-pituitary-adrenocortical (HPA) axis and self-regulate through negative feedback. Negative feedback occurs on a rapid time scale is thought act nongenomic mechanisms. In these studies, we investigated fast inhibition of HPA stress responses by direct glucocorticoid action at paraventricular nucleus hypothalamus (PVN). Local infusion dexamethasone or membrane-impermeant dexamethasone-BSA conjugate into PVN rapidly inhibits restraint-induced ACTH corticosterone release manner consistent with actions cell membrane. The blocked cannabinoid CB1 receptor antagonist AM-251, suggesting requires local endocannabinoids. Hypothalamic tissue content endocannabinoid 2-arachidonoyl glycerol elevated restraint stress, processes. These data support hypothesis glucocorticoid-induced mediated signaling mechanism involves level PVN.