title: Regulation of corticotropin-releasing factor and its types 1 and 2 receptors by leptin in rats subjected to treadmill running-induced stress.
abstract: The present study was conducted to investigate the long-term effects of subchronic elevation of central leptin levels on the expression of corticotropin-releasing factor (CRF) and its types 1 and 2 receptors in the brain of rats subjected to treadmill running-induced stress. PBS or recombinant murine leptin was infused continuously for a period of 5 days into the third ventricle of rats with the aid of osmotic minipumps at a delivery rate of 2 mug/day. On the fifth day of infusion, rats were killed under resting conditions or after a session of treadmill running, which is known to induce a stress response in rats. Leptin treatment significantly decreased food intake, body weight, white adipose tissue weight, glucose and insulin plasma contents, and blunted the treadmill running-induced elevation in plasma levels of corticosterone. Leptin infusion prevented stress-induced de novo synthesis of CRF in the paraventricular hypothalamic nucleus (PVN), which was measured using the intronic probe for CRF heteronuclear RNA. The induction of the type 1 CRF receptor (CRF(1)R) in the PVN and supraoptic nucleus in running rats was also significantly blunted by leptin. In contrast, leptin treatment strongly increased the expression of type 2 CRF receptor (CRF(2)R) in the ventromedial hypothalamic nucleus (VMH). The present results suggest that subchronic elevation of central levels of leptin blunts treadmill running-induced activation of the hypothalamic-pituitary-adrenal axis through the inhibition of activation of the CRFergic PVN neurons, and potentially enhances the anorectic CRF effects via the stimulation of expression of CRF(2)R in the VMH.
authors.affiliation: Laval Hospital Research Center and Merck-Frosst/IRSC Obesity Research Chair, 2725 chemin Sainte-Foy, Québec, Canada.
authors.forename: Qingling
authors.initials: Q
authors.lastname: Huang
authors.forename: Elena
authors.initials: E
authors.lastname: Timofeeva
authors.forename: Denis
authors.initials: D
authors.lastname: Richard
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D000855:Anorexia / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D007090:Image Interpretation, Computer-Assisted; D017403:In Situ Hybridization / Q000379:methods; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D012420:Running; D013312:Stress, Physiological / Q000378:metabolism*; D014697:Ventromedial Hypothalamic Nucleus / Q000737:chemistry / Q000378:metabolism; D000099052:CRF Receptor, Type 1
chemical_list: D001786:Blood Glucose; C101531:CRF receptor type 2; D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone