Regulation of human epidermal melanocyte biology by beta-endorphin.
beta-Endorphin is an opioid peptide cleaved from the precursor pro-hormone pro-opiomelanocortin, from which other peptides such as adrenocorticotropic hormone, beta-lipotropic hormone, and alpha-melanocyte-stimulating hormone are also derived. alpha-Melanocyte-stimulating hormone and adrenocorticotropic hormone are well documented to regulate human skin pigmentation via action at the melanocortin-1 receptor. Whereas plasma beta-endorphin is reported to increase after exposure to ultraviolet radiation, to date a functional role for beta-endorphin in the regulation of human epidermal melanocyte biology has not been demonstrated. This study was designed to examine the involvement of the beta-endorphin/mu-opiate receptor system in human epidermal melanocytes. To address this question we employed reverse transcription-polymerase chain reaction, and immunohistochemistry/cytochemistry and immunoelectron microscopy using beta-endorphin and mu-opiate receptor specific antibodies. A functional role for beta-endorphin was assessed in epidermal melanocyte cultures by direct stimulation with the peptide. This study demonstrated the expression of mu-opiate receptor mRNA in cultured epidermal melanocytes, as well as mRNA for pro-opiomelanocortin. In addition, we have shown that beta-endorphin and mu-opiate receptor are expressed at the protein level in situ in glycoprotein100-positive melanocytes. The expression of both beta-endorphin and mu-opiate receptor correlated positively with their differentiation status in vitro. Furthermore, immunoelectron microscopy studies revealed an association of beta-endorphin with melanosomes. Functional studies showed that beta-endorphin has potent melanogenic, mitogenic, and dendritogenic effects in cultured epidermal melanocytes deprived of any exogenous supply of pro-opiomelanocortin peptides. Thus, we report that human epidermal melanocytes express a fully functioning beta-endorphin/mu-opiate receptor system. In the absence of any data showing cross-talk between the mu-opiate receptor and the melanocortin-1 receptor, we conclude that the beta-endorphin/mu-opiate receptor system participates in the regulation of skin pigmentation.
Kauser
Söbia
S
Department of Biomedical Sciences, University of Bradford, West Yorkshire, UK.
Schallreuter
Karin U
KU
Thody
Anthony J
AJ
Gummer
Christopher
C
Tobin
Desmond J
DJ
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003712:Dendrites / Q000648:ultrastructure; D000078404:Epidermal Cells; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D020460:Melanosomes / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics; D014018:Tissue Distribution; D001615:beta-Endorphin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D008543:Melanins; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin