title: Melatonin and its metabolites accumulate in the human epidermis in vivo and inhibit proliferation and tyrosinase activity in epidermal melanocytes in vitro.
abstract: Melatonin and its metabolites including 6-hydroxymelatonin (6(OH)M), N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) and 5-methoxytryptamine (5MT) are endogenously produced in human epidermis. This production depends on race, gender and age. The highest melatonin levels are in African-Americans. In each racial group they are highest in young African-Americans [30-50 years old (yo)], old Caucasians (60-90 yo) and Caucasian females. AFMK levels are the highest in African-Americans, while 6(OH)M and 5MT levels are similar in all groups. Testing of their phenotypic effects in normal human melanocytes show that melatonin and its metabolites (10(-5) M) inhibit tyrosinase activity and cell growth, and inhibit DNA synthesis in a dose dependent manner with 10(-9) M being the lowest effective concentration. In melanoma cells, they inhibited cell growth but had no effect on melanogenesis, except for 5MT which enhanced L-tyrosine induced melanogenesis. In conclusion, melatonin and its metabolites [6(OH)M, AFMK and 5MT] are produced endogenously in human epidermis and can affect melanocyte and melanoma behavior.
authors.affiliation: Departments of Pathology and Laboratory Medicine, Division of Rheumatology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Tae-Kang
authors.initials: TK
authors.lastname: Kim
authors.affiliation: Departments of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Zongtao
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Departments of Pathology and Laboratory Medicine, Division of Rheumatology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Tidwell
authors.affiliation: Departments of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: We
authors.initials: W
authors.lastname: Li
authors.affiliation: Departments of Pathology and Laboratory Medicine, Division of Rheumatology, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Department of Dermatology. University of Alabama Birmingham, Birmingham, AL 35294. Electronic address: aslominski@uthsc.edu.
authors.forename: Andrzej T
authors.initials: AT
authors.lastname: Slominski
mesh_terms: D008735:5-Methoxytryptamine / Q000378:metabolism* / Q000494:pharmacology; D000328:Adult; D001741:Black or African American; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D002478:Cells, Cultured; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007735:Kynuramine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008544:Melanocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism; D008550:Melatonin / Q000031:analogs & derivatives / Q000378:metabolism*; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012737:Sex Factors; D012878:Skin Neoplasms / Q000378:metabolism; D044465:White People
chemical_list: D007735:Kynuramine; D008735:5-Methoxytryptamine; C041550:N-acetyl-N-formyl-5-methoxykynurenamine; D011505:Protein-Tyrosine Kinases; D008550:Melatonin; C012365:6-hydroxymelatonin
keywords: 5-methoxytryptamine; 6-hydroxymelatonin; AFMK; Epidermis; Melanocytes; Melatonin