Document Detail

Melanocortin 4 receptor distribution in the human hypothalamus.
MedLine Citation:
PMID:  23211571     Owner:  NLM     Status:  MEDLINE    
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.
DESIGN AND 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.
CONCLUSION: Expression of MC4R mRNA in the human hypothalamus is widespread and in close approximation to endogenous MC4R binding partners AgRP and α-MSH.
Jacqueline E Siljee; Unga A Unmehopa; Andries Kalsbeek; Dick F Swaab; Eric Fliers; Anneke Alkemade
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-02-15
Journal Detail:
Title:  European journal of endocrinology / European Federation of Endocrine Societies     Volume:  168     ISSN:  1479-683X     ISO Abbreviation:  Eur. J. Endocrinol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-18     Completed Date:  2013-04-08     Revised Date:  2013-05-08    
Medline Journal Info:
Nlm Unique ID:  9423848     Medline TA:  Eur J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  361-9     Citation Subset:  IM    
Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Room G2-118, 1105 AZ Amsterdam, The Netherlands.
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MeSH Terms
Aged, 80 and over
Agouti-Related Protein / metabolism
Basal Nucleus of Meynert / metabolism,  pathology
Gene Expression Regulation*
Hypothalamus / metabolism*,  pathology
In Situ Hybridization
Middle Aged
Nerve Tissue Proteins / genetics,  metabolism*
Neurons / metabolism*,  pathology
Organ Specificity
Paraventricular Hypothalamic Nucleus / metabolism,  pathology
RNA, Messenger / metabolism
Receptor, Melanocortin, Type 4 / genetics,  metabolism*
Supraoptic Nucleus / metabolism,  pathology
alpha-MSH / genetics
Reg. No./Substance:
0/AGRP protein, human; 0/Agouti-Related Protein; 0/Ligands; 0/MC4R protein, human; 0/Nerve Tissue Proteins; 0/RNA, Messenger; 0/Receptor, Melanocortin, Type 4; 581-05-5/alpha-MSH

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