title: Cholesterol regulates melanogenesis in human epidermal melanocytes and melanoma cells.
abstract: Cholesterol is important for membrane stability and is the key substrate for the synthesis of steroid hormones and vitamin D. Furthermore, it is a major component of the lipid barrier in the stratum corneum of the human epidermis. Considering that steroid hormone synthesis is taking place in epidermal melanocytes, we tested whether downstream oestrogen receptor/cAMP signalling via MITF/tyrosine hydroxylase/tyrosinase/pigmentation could be possibly modulated by cholesterol. For this purpose, we utilized human primary melanocyte cell cultures and human melanoma cells with different pigmentation capacity applying immunofluorescence, RT-PCR, Western blotting and determination of melanin content. Our in situ and in vitro results demonstrated that melanocytes can synthesize cholesterol via HMG-CoA reductase and transport cholesterol via LDL/Apo-B100/LDLR. Moreover, we show that cholesterol increases melanogenesis in these cells and in human melanoma cells of intermediate pigmentation (FM55) in a time- and dose-dependent manner. Cellular cholesterol levels in melanoma cells with different pigmentation patterns, epidermal melanocytes and keratinocytes do not differ except in the amelanotic (FM3) melanoma cell line. This result is in agreement with decreasing cholesterol content versus increasing pigmentation in melanosomes. Cholesterol induces cAMP in a biphasic manner i.e. after 30 min and later after 6 and 24 h, meanwhile protein expression of oestrogen receptor beta, CREB, MITF, tyrosine hydroxylase and tyrosinase is induced after 72 h. Taken together, we show that human epidermal melanocytes have the capacity of cholesterol signalling via LDL/Apo-B100/LDL receptor and that cholesterol under in vitro conditions increases melanogenesis.
authors.affiliation: Clinical and Experimental Dermatology, Division of Biomedical Sciences, School of Life Sciences, University of Bradford, Bradford BD7 1DP, UK. k.schallreuter@bradford.ac.uk
authors.forename: Karin U
authors.initials: KU
authors.lastname: Schallreuter
authors.forename: Sybille
authors.initials: S
authors.lastname: Hasse
authors.forename: Hartmut
authors.initials: H
authors.lastname: Rokos
authors.forename: Bhaven
authors.initials: B
authors.lastname: Chavan
authors.forename: Mohamed
authors.initials: M
authors.lastname: Shalbaf
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Spencer
authors.forename: John M
authors.initials: JM
authors.lastname: Wood
mesh_terms: D053299:Apolipoprotein B-100 / Q000378:metabolism; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D000078404:Epidermal Cells; D006801:Humans; D008544:Melanocytes / Q000166:cytology*; D008545:Melanoma / Q000473:pathology*; D008954:Models, Biological; D010858:Pigmentation; D011960:Receptors, Estrogen / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D013997:Time Factors; D014807:Vitamin D / Q000378:metabolism
chemical_list: D053299:Apolipoprotein B-100; D011960:Receptors, Estrogen; D011973:Receptors, LDL; D014807:Vitamin D; D002784:Cholesterol; D000242:Cyclic AMP