Differential Regulation of Melanin-Concentrating Hormone and Orexin Genes in the Agouti-Related protein/melanocortin-4 Receptor System

Biochem Biophys Res Commun. 2000 Feb 5;268(1):88-91. doi: 10.1006/bbrc.1999.2081.

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.

MeSH terms

  • Agouti Signaling Protein
  • Agouti-Related Protein
  • Animals
  • Eating / drug effects
  • Eating / physiology
  • Gene Expression Regulation / drug effects
  • Hypothalamic Hormones / genetics*
  • Hypothalamus / drug effects
  • Hypothalamus / physiology
  • Injections, Intraventricular
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Melanins / genetics*
  • Melanocyte-Stimulating Hormones / administration & dosage
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Neuropeptides / genetics*
  • Pituitary Hormones / genetics*
  • Proteins / administration & dosage
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Melanocortin, Type 4
  • Receptors, Peptide / antagonists & inhibitors
  • Receptors, Peptide / metabolism*
  • Signal Transduction
  • alpha-MSH / administration & dosage

Substances

  • AGRP protein, rat
  • Agouti Signaling Protein
  • Agouti-Related Protein
  • Agrp protein, mouse
  • Asip protein, rat
  • Hypothalamic Hormones
  • Intercellular Signaling Peptides and Proteins
  • Melanins
  • Neuropeptides
  • Pituitary Hormones
  • Proteins
  • RNA, Messenger
  • Receptor, Melanocortin, Type 4
  • Receptors, Peptide
  • a protein, mouse
  • SHU 9119
  • alpha-MSH
  • melanin-concentrating hormone
  • Melanocyte-Stimulating Hormones