Dexamethasone blocks the refeeding-induced phosphorylation of cAMP response element-binding protein in the rat hypothalamus.
We previously reported that dexamethasone pretreatment abolishes the refeeding-induced neuronal nitric oxide synthase (nNOS) expression in the rat paraventricular nucleus (PVN). It was reported that nNOS upstream carries cAMP response element (CRE) and nNOS expression is mediated by a CRE-binding protein (CREB)-dependent mechanism. In this study, CREB phosphorylation was co-localized in the nNOS neurons of the rat PVN regardless of feeding conditions. The relative amount of phosphorylated CREB in the hypothalamic tissue lysates increased by 1 h of refeeding following 48 h of food deprivation, and interestingly, this increase was blocked by dexamethasone administration before the food onset. These results suggest that glucocorticoids exert an inhibitory role in CREB phosphorylation directed by nutritional stimuli in the rat hypothalamus, and this inhibition may be related to nNOS gene expression in this brain region.
Lee
Joo Young
JY
Department of Pharmacology and Yonsei Brain Research Institute, BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Lee
Jong-Ho
JH
Kim
Dong Goo
DG
Jahng
Jeong Won
JW
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology*; D004435:Eating; D005508:Food Deprivation; D005938:Glucocorticoids / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D017362:Cyclic AMP Response Element-Binding Protein; D005938:Glucocorticoids; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat