Cultured human melanocytes respond to MSH peptides and ACTH.
Although the administration of melanocyte-stimulating hormone (MSH) peptides results in skin darkening in man, cultured human melanocytes have been reported to be unresponsive to these peptides. This may be a consequence of the conditions under which the cells were maintained in vitro, particularly the use of phorbol esters and cholera toxin as melanocyte mitogens. By culturing the cells in the absence of these additives, we demonstrate that alpha-MSH and its synthetic analogue Nle4DPhe7 alpha-MSH (NDP-MSH) induce dose-related increases in melanin content and tyrosinase activity and affect cell morphology in the majority of human melanocyte cultures. In addition, NDP-MSH induces increases in tyrosinase mRNA and tyrosinase-related protein-1 (TRP-1) mRNA. The dose-response curves for the MSH peptides are sigmoidal and the two peptides are equipotent in their effects on human melanocytes. Adrenocorticotropic hormone (ACTH) also affects morphology and stimulates melanogenesis and tyrosinase activity in human melanocytes. However, the dose-response curves for ACTH are biphasic, and the melanocytes respond to lower concentrations of ACTH than MSH peptides, similar to those normally present in human plasma. These findings may be important in understanding the role of these pro-opiomelanocortin peptides in human skin pigmentation.
Department of Dermatology, University of Newcastle upon Tyne, United Kingdom.
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Hunt
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Donatien
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Lunec
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Todd
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Kyne
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D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008543:Melanins / Q000378:metabolism; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000494:pharmacology
D008543:Melanins; D008562:Membrane Glycoproteins; D011506:Proteins; D012333:RNA, Messenger; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; D000242:Cyclic AMP; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase