Fast feedback inhibition of the HPA axis by glucocorticoids is mediated by endocannabinoid signaling. Endocrinology 2010 Oct;151(10):4811-9
Date
08/13/2010Pubmed ID
20702575Pubmed Central ID
PMC2946139DOI
10.1210/en.2010-0285Scopus ID
2-s2.0-77957276332 (requires institutional sign-in at Scopus site) 281 CitationsAbstract
Glucocorticoid hormones are secreted in response to stimuli that activate the hypothalamo-pituitary-adrenocortical (HPA) axis and self-regulate through negative feedback. Negative feedback that occurs on a rapid time scale is thought to act through nongenomic mechanisms. In these studies, we investigated fast feedback inhibition of HPA axis stress responses by direct glucocorticoid action at the paraventricular nucleus of the hypothalamus (PVN). Local infusion of dexamethasone or a membrane-impermeant dexamethasone-BSA conjugate into the PVN rapidly inhibits restraint-induced ACTH and corticosterone release in a manner consistent with feedback actions at the cell membrane. The dexamethasone fast feedback response is blocked by the cannabinoid CB1 receptor antagonist AM-251, suggesting that fast feedback requires local release of endocannabinoids. Hypothalamic tissue content of the endocannabinoid 2-arachidonoyl glycerol is elevated by restraint stress, consistent with endocannabinoid action on feedback processes. These data support the hypothesis that glucocorticoid-induced fast feedback inhibition of the HPA axis is mediated by a nongenomic signaling mechanism that involves endocannabinoid signaling at the level of the PVN.
Author List
Evanson NK, Tasker JG, Hill MN, Hillard CJ, Herman JPAuthor
Cecilia J. Hillard PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCannabinoid Receptor Modulators
Dexamethasone
Endocannabinoids
Feedback, Physiological
Glucocorticoids
Humans
Hypothalamo-Hypophyseal System
Hypothalamus
Injections, Intraventricular
Male
Pituitary-Adrenal System
Rats
Rats, Sprague-Dawley
Restraint, Physical
Signal Transduction
Stress, Psychological
Time Factors
