title: A fully functional proopiomelanocortin/melanocortin-1 receptor system regulates the differentiation of human scalp hair follicle melanocytes.
abstract: The proopiomelanocortin (POMC)-derived peptides, ACTH and alpha-MSH, are the principal mediators of human skin pigmentation via their action at the melanocortin-1 receptor (MC-1R). Recent data have demonstrated the existence of a functionally active beta-endorphin/mu-opiate receptor system in both epidermal and hair follicle melanocytes, whereby beta-endorphin can regulate melanogenesis, dendricity, and proliferation in these cells. However, a role for ACTH and alpha-MSH in the regulation of the human follicular pigmentary unit has not been determined. This study was designed to examine the involvement of ACTH and the alpha-MSH/MC-1R system in human follicular melanocyte biology. To address this question we employed RT-PCR and immunohisto/cytochemistry, and a functional role for these POMC peptides was assessed in follicular melanocyte cultures. Human scalp hair follicle melanocytes synthesized and processed POMC. ACTH and alpha-MSH in association with their processing enzymes and MC-1R are expressed in human follicular melanocytes at the message level in vitro and at the protein level both in situ and in vitro. The expression of the POMC/MC-1R receptor system was confined only to subpopulations of poorly and moderately differentiated melanocytes. In addition, functional studies revealed that ACTH and alpha-MSH are able to promote follicular melanocyte differentiation by up-regulating melanogenesis, dendricity, and proliferation in less differentiated melanocyte subpopulations. Thus, these findings suggest a role for these POMC peptides in regulating human hair follicle melanocyte differentiation.
authors.affiliation: Department of Biomedical Sciences, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom.
authors.forename: Söbia
authors.initials: S
authors.lastname: Kauser
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Thody
authors.forename: Karin U
authors.initials: KU
authors.lastname: Schallreuter
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Gummer
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Tobin
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D018859:Hair Follicle / Q000166:cytology*; D006801:Humans; D008544:Melanocytes / Q000166:cytology* / Q000502:physiology*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D051859:Neuroendocrine Secretory Protein 7B2; D010907:Pituitary Hormones / Q000235:genetics; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism; D045664:Proprotein Convertase 1 / Q000235:genetics; D045706:Proprotein Convertase 2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics; D012535:Scalp / Q000166:cytology; D000521:alpha-MSH / Q000235:genetics* / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D010907:Pituitary Hormones; D012333:RNA, Messenger; D044102:Receptor, Melanocortin, Type 1; C497678:SCG5 protein, human; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2