Differential regulation of melanin-concentrating hormone and orexin genes in the agouti-related protein/melanocortin-4 receptor system.
Agouti protein and agouti-related protein (AGRP) antagonize alpha-melanocyte-stimulating hormone that binds to and activates the melanocortin-4 receptor (MC4-R) in the hypothalamus, thereby stimulating food intake. Melanin-concentrating hormone (MCH) and orexin are orexigenic peptides that specifically are synthesized in the lateral hypothalamus. MCH gene expression was augmented in A(y)/a (agouti) mice which overexpress agouti protein, but orexin mRNA was not. AGRP administered intracerebroventricularly into wild-type rats augmented MCH but not orexin gene expression. Also, SHU9119, a peptidergic antagonist of MC4-R, increased only MCH mRNA. These findings indicate that interruption of signaling at MC4-R activates the MCH but not the orexin gene. The biosyntheses of MCH and orexin are regulated through different pathways.
Hanada
R
R
Department of Internal Medicine I, School of Medicine, Oita Medical University, Oita, 879-5593, Japan.
Nakazato
M
M
Matsukura
S
S
Murakami
N
N
Yoshimatsu
H
H
Sakata
T
T
D054366:Agouti Signaling Protein; D054369:Agouti-Related Protein; D000818:Animals; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D007028:Hypothalamic Hormones / Q000235:genetics*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008543:Melanins / Q000235:genetics*; D009074:Melanocyte-Stimulating Hormones / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009479:Neuropeptides / Q000235:genetics*; D010907:Pituitary Hormones / Q000235:genetics*; D011506:Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D000521:alpha-MSH / Q000008:administration & dosage
C515197:AGRP protein, rat; D054366:Agouti Signaling Protein; D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; C515184:Asip protein, rat; D007028:Hypothalamic Hormones; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins; D009479:Neuropeptides; D010907:Pituitary Hormones; D011506:Proteins; D012333:RNA, Messenger; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide; C515183:a protein, mouse; C103272:SHU 9119; D000521:alpha-MSH; C019463:melanin-concentrating hormone; D009074:Melanocyte-Stimulating Hormones