Role of central glucagon-like peptide-1 in hypothalamo-pituitary-adrenocortical facilitation following chronic stress.
Central glucagon-like peptide-1 (GLP-1) regulates food intake, glucose homeostasis, and behavioral and neuroendocrine responses to acute stress. Given its pronounced role in acute stress regulation, the GLP-1 system is a prime candidate for mediating the prolonged drive of the hypothalamo-pituitary-adrenocortical axis by chronic stress. To test this hypothesis, we evaluated the necessity and sufficiency of GLP-1 for production of chronic stress-induced changes in HPA axis function. Exogenous GLP-1 or the GLP-1 receptor antagonist, dHG-exendin, were delivered into the 3rd ventricle of control animals or animals exposed to chronic variable stress (CVS) for 7 days. Animals in the CVS groups received GLP-1 or dHG-exendin immediately prior to each stress exposure. Prior to and at the end of the 7-day trial, chronically-stressed animals were subjected to a novel stressor to test for HPA axis facilitation. Neither GLP-1 nor dHG-exendin affected CVS-associated increases in adrenal weight or decreases in basal plasma glucose levels. In addition, neither exogenous GLP-1 nor dHG-exendin altered any index of HPA axis activity in unstressed rats. However, GLP-1 enhanced CVS-induced facilitation of corticosterone (but not ACTH) response to an acute stress, whereas dHG-exendin inhibited facilitation. In addition, GLP-1 decreased body weight in chronically-stressed animals. dHG-exendin increased food intake and body weight in unstressed animals, consistent with a tonic role for GLP-1 in body weight regulation. Overall, our data suggest that brain GLP-1 modulates HPA axis activity within the context of chronic stress, perhaps at the level of the adrenal gland.
Tauchi
Miyuki
M
Neuroscience Graduate Program, Department of Psychiatry, University of Cincinnati, 2170 East Galbraith Road, Cincinnati, OH 45237-0506, USA.
Zhang
Rong
R
D'Alessio
David A
DA
Seeley
Randy J
RJ
Herman
James P
JP
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage*; D006025:Glycosaminoglycans / Q000008:administration & dosage; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000379:methods; D013315:Stress, Psychological / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control
D006025:Glycosaminoglycans; C106156:depolymerized holothurian glucosaminoglycan; D052216:Glucagon-Like Peptide 1; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone