Orexin expression and function: glucocorticoid manipulation, stress, and feeding studies.
We investigated the effects of glucocorticoid manipulation on orexin-A-induced feeding and prepro-orexin mRNA levels in the lateral hypothalamic area (LHA) of the rat brain. Adrenalectomy (ADX) reduced orexin-A-induced feeding over 4 h by about 60%, compared with shams, an effect that was reversed by corticosterone (CORT) replacement. ADX had no effect on prepro-orexin mRNA levels in the LHA in either the morning or the evening; however, message was up-regulated by CORT in the morning but not the evening. An increased number of emulsion grains per cell in the LHA suggests that this is a specific increase in prepro-orexin mRNA and is not due to an increased number of cells expressing message. Prepro-orexin mRNA levels in the LHA were elevated 4 h after injection of lipopolysaccharide, compared with saline-injected controls. Partial but not complete abolition of orexin-A-induced feeding by ADX suggests that orexin-A-induced feeding may be mediated through glucocorticoid-dependent and glucocorticoid-independent pathways. In the morning increased prepro-orexin mRNA after CORT replacement demonstrates that orexin expression is sensitive to increased concentrations of glucocorticoids. However, the lack of effect of ADX on prepro-orexin mRNA levels suggests that endogenous glucocorticoids are not involved in tonic regulation of basal prepro-orexin expression. Overall our data constitute a body of evidence for an integrated relationship between central orexin expression, stress, glucocorticoid manipulation, and feeding patterns in the rat.
Ford
Gemma K
GK
Henry Wellcome Laboratory for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, United Kingdom.
Al-Barazanji
Kamal A
KA
Wilson
Shelagh
S
Jones
Declan N C
DN
Harbuz
Michael S
MS
Jessop
David S
DS
D000315:Adrenalectomy; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000494:pharmacology; D002940:Circadian Rhythm / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism* / Q000494:pharmacology; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009479:Neuropeptides / Q000235:genetics* / Q000494:pharmacology; D000068797:Orexins; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000503:physiopathology*
D000893:Anti-Inflammatory Agents; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D009479:Neuropeptides; D000068797:Orexins; D012333:RNA, Messenger; D003345:Corticosterone