title: Melanocortin 4 receptor distribution in the human hypothalamus.
abstract: OBJECTIVE
  The melanocortin 4 receptor (MC4R) is an essential regulator of energy homeostasis and metabolism, and MC4R mutations represent the most prevalent monogenetic cause of obesity in humans known to date. Hypothalamic MC4Rs in rodents are well characterized in neuroanatomical and functional terms, but their expression pattern in the human hypothalamus is unknown.
  
  
  METHODS
  To determine the topographic distribution and identity of cells expressing MC4R mRNA in the human hypothalamus, locked nucleic acid in situ hybridization was performed on nine human postmortem hypothalami. In addition, co-expression of MC4R with glial fibrillary acidic protein (GFAP), vasopressin/oxytocin (AVP/OXT), corticotropin-releasing hormone (CRH), neuropeptide Y (NPY), agouti-related protein (AgRP), and α-melanocyte stimulating hormone (α-MSH) was examined.
  
  
  RESULTS
  Most intense MC4R mRNA expression was present in the paraventricular nucleus (PVN), the supraoptic nucleus (SON), and the nucleus basalis of Meynert. Most MC4R-positive cells in the SON also expressed AVP/OXT. Co-expression with AVP/OXT in the PVN was less abundant. We did not observe co-expression of MC4R mRNA and GFAP, CRH, NPY, AgRP, or α-MSH. However, fiber-like staining of NPY, AgRP, and α-MSH was found adjacent to MC4R-positive cells in the PVN.
  
  
  CONCLUSIONS
  Expression of MC4R mRNA in the human hypothalamus is widespread and in close approximation to endogenous MC4R binding partners AgRP and α-MSH.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Room G2-118, 1105 AZ Amsterdam, The Netherlands. siljeej@gmail.com
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Siljee
authors.forename: Unga A
authors.initials: UA
authors.lastname: Unmehopa
authors.forename: Andries
authors.initials: A
authors.lastname: Kalsbeek
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
authors.forename: Anneke
authors.initials: A
authors.lastname: Alkemade
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054369:Agouti-Related Protein / Q000378:metabolism; D020532:Basal Nucleus of Meynert / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000378:metabolism*; D013495:Supraoptic Nucleus / Q000378:metabolism / Q000473:pathology; D000521:alpha-MSH / Q000235:genetics
chemical_list: C515198:AGRP protein, human; D054369:Agouti-Related Protein; D008024:Ligands; C470072:MC4R protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D044105:Receptor, Melanocortin, Type 4; D000521:alpha-MSH