Central actions of CRF on thermogenesis are mediated by pro-opiomelanocortin products.
Corticotrophin-releasing factor (CRF) causes central activation of thermogenesis. The aim of this study was to investigate whether this action is mediated by ACTH or other peptides derived from the ACTH precursor pro-opiomelanocortin (POMC) within the CNS. Central (intracerebroventricular) injection of rat CRF caused dose-dependent increases in resting oxygen consumption (VO2) in conscious rats (maximal 26 +/- 5% at 2 nmol CRF). These responses were significantly attenuated by pretreatment (i.c.v.) with either a monoclonal antibody raised to gamma 1MSH or with naloxone which antagonises beta-endorphin (beta-EP) actions. The increases were not affected by pretreatment with monoclonal antibodies to ACTH or the N-terminal of POMC. Central injections of gamma 1-melanocyte-stimulating hormone (MSH) or beta-EP caused dose-dependent increases in VO2 (maximal at 0.5-1.5 pmol) and these were markedly inhibited by pretreatment with the anti-gamma 1-MSH antibody or naloxone respectively. Injection of ACTH or alpha MSH did not significantly affect VO2 at doses up to 2 nmol. These data indicate that the central actions of CRF on thermogenesis may be mediated, at least in part, by release of gamma MSH and/or beta-EP.
Rothwell
N J
NJ
Department of Physiological Sciences, University of Manchester, UK.
Hardwick
A
A
LeFeuvre
R A
RA
Crosby
S R
SR
White
A
A
D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007267:Injections; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000145:classification / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D051381:Rats; D001615:beta-Endorphin / Q000494:pharmacology
D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D009074:Melanocyte-Stimulating Hormones; D003346:Corticotropin-Releasing Hormone