Abstract
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.
Copyright 2000 Academic Press.
MeSH terms
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Agouti Signaling Protein
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Agouti-Related Protein
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Animals
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Eating / drug effects
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Eating / physiology
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Gene Expression Regulation / drug effects
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Hypothalamic Hormones / genetics*
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Hypothalamus / drug effects
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Hypothalamus / physiology
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Injections, Intraventricular
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Intercellular Signaling Peptides and Proteins
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Male
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Melanins / genetics*
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Melanocyte-Stimulating Hormones / administration & dosage
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Neuropeptides / genetics*
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Pituitary Hormones / genetics*
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Proteins / administration & dosage
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Proteins / genetics
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Proteins / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Receptor, Melanocortin, Type 4
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Receptors, Peptide / antagonists & inhibitors
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Receptors, Peptide / metabolism*
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Signal Transduction
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alpha-MSH / administration & dosage
Substances
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AGRP protein, rat
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Agouti Signaling Protein
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Agouti-Related Protein
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Agrp protein, mouse
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Asip protein, rat
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Hypothalamic Hormones
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Intercellular Signaling Peptides and Proteins
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Melanins
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Neuropeptides
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Pituitary Hormones
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Proteins
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RNA, Messenger
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Receptor, Melanocortin, Type 4
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Receptors, Peptide
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a protein, mouse
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SHU 9119
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alpha-MSH
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melanin-concentrating hormone
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Melanocyte-Stimulating Hormones