Pro-opiomelanocortin-related peptides, prohormone convertases 1 and 2 and the regulatory peptide 7B2 are present in melanosomes of human melanocytes.
Recently, it has been shown that alpha-melanocyte stimulating hormone can directly activate tyrosinase by removing the allosteric regulator 6(R)-L-erythro 5,6,7,8 tetrahydrobiopterin resulting in a stable alpha-melanocyte stimulating hormone/6(R)-L-erythro 5,6,7,8 tetrahydrobiopterin complex. As melanin production occurs in the melanosome, a specific organelle of the melanocyte, it seemed important to investigate whether these organelles themselves actually produce pro-opiomelanocortin-related peptides in their acidic environment. The presence of alpha-melanocyte stimulating hormone and adrenocorticotropin in the epidermis and melanocytes has been shown by several investigators. In order to follow possible pro-opiomelanocortin processing in the melanosome, human melanocytes were established in MCDB 153 medium and utilized for immunohistochemistry, immunogold electron microscopy, and western blotting. For this purpose antibodies against alpha-melanocyte stimulating hormone, adrenocorticotropin, prohormone convertases 1 and 2 (PC1 and PC2) and the PC2 regulatory protein 7B2 were used. Our results demonstrated the presence of the entire system for pro-opiomelanocortin processing in the melanosome. Considering the pH optima of these convertases, the results are in agreement with an autocrine intramelanosomal production of pro- opiomelanocortin-related peptides and an autocrine production and recycling of the cofactor 6(R)-L- erythro 5,6,7,8 tetrahydrobiopterin in melanocytes. Based on these novel observations, we would like to propose that the pigmentation process may not necessarily involve a melanocortin-1 receptor-mediated mechanism.
Peters
E M
EM
Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, West Yorkshire, UK.
Tobin
D J
DJ
Seidah
N G
NG
Schallreuter
K U
KU
D015153:Blotting, Western; D006801:Humans; D008544:Melanocytes / Q000648:ultrastructure; D020460:Melanosomes / Q000737:chemistry*; D016253:Microscopy, Immunoelectron; D009419:Nerve Tissue Proteins / Q000032:analysis*; D051859:Neuroendocrine Secretory Protein 7B2; D010907:Pituitary Hormones / Q000032:analysis*; D011333:Pro-Opiomelanocortin / Q000032:analysis*; D045706:Proprotein Convertase 2; D013381:Subtilisins / Q000032:analysis*; D000521:alpha-MSH / Q000032:analysis
D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D010907:Pituitary Hormones; C497678:SCG5 protein, human; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D013381:Subtilisins; D045706:Proprotein Convertase 2