Rabbit Anti-Human MC5R (N-terminal) Polyclonal antibody

Background: The melanocortin receptor-5 (MC5R) is present in human sebaceous glands, where it is expressed in differentiated sebocytes only. The targeted disruption of MC5R in mice resulted in reduced sebaceous lipid production and a severe defect in water repulsion. Objective: To investigate the physiological function of MC5R in human sebaceous glands. Methods: A novel MC1R and MC5R antagonist (JNJ-10229570) was used to treat primary human sebaceous cells or human skins grafted onto severe combined immunodeficient (SCID) mice. Transcription profiling, lipid analyses, and histological and immunohistochemical staining were used to analyze the effect of MC5R inhibition on sebaceous gland differentiation and sebum production. Results: JNJ-10229570 dose dependently inhibited the production of sebaceous lipids in cultured primary human sebocytes. Topical treatment with JNJ-10229570 of human skins transplanted onto SCID mice resulted in a marked decrease in sebum-specific lipid production, sebaceous gland's size and the expression of the sebaceous differentiation marker epithelial-membrane antigen (EMA). Treatment with flutamide, a known inhibitor of sebum production, gave similar results, validating the human skin/SCID mouse experimental system for sebaceous secretion studies. Conclusion: Our data suggest that antagonists of MC1R and MC5R could be effective sebum suppressive agents and might have a potential for the treatment of acne and other sebaceous gland pathologies. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

The melanocortin receptors (MCR) belong to the superfamily of G-protein-coupled receptors that participate in both peripheral and central functions, including regulation of energy balance. Genomic clones of the five chicken (GGA) MCRs were isolated and used to find the chromosomal location of each of the loci. The genes encoding MC2R and MC5R mapped to the middle part of the long arm of chromosome 2 (GGA2q22-q26) and MC4R proximally on the same chromosome arm, close to the centromere (2q12). This arrangement seems to be conserved on chromosome 18 in the human (HSA18). The MC1R and MC3R genes mapped to different microchromosomes that also appear to share homology with the respective human localization. The conserved synteny of the MC2R, MC5R, and MC4R cluster in chicken (GGA2), human (HSA18), and other mammals suggests that this cluster is ancient and was formed by local gene duplications that most likely occurred early in vertebrate evolution. Analysis of conserved synteny with mammalian genomes and paralogon segments prompted us to predict an ancestral gene organization that may explain how this family was formed through both local duplication and tetraploidization processes. (C) 2003 Elsevier Science (USA). All rights reserved.