title: Differentiation of murine melanocyte precursors induced by 1,25-dihydroxyvitamin D3 is associated with the stimulation of endothelin B receptor expression.
abstract: The effects of 1,25-dihydroxyvitamin D3 on the differentiation of immature melanocyte precursors were studied. The NCC-/melb4 cell line is an immature melanocyte cell line established from mouse neural crest cells. 1,25-Dihydroxyvitamin D3 inhibited the growth of NCC-/melb4 cells at concentrations higher than 10(-8) m. That growth inhibition was accompanied by the induction of tyrosinase and a change in L-3,4-dihydroxyphenylalanine reactivity from negative to positive. Electron microscopy demonstrated that melanosomes were in more advanced stages after 1,25-dihydroxyvitamin D3 treatment. In primary cultures of murine neural crest cells, L-3,4-dihydroxyphenylalanine-positive cells were increased after 1,25-dihydroxyvitamin D3 treatment. These findings indicate that 1,25-dihydroxyvitamin D3 stimulates the differentiation of immature melanocyte precursors. Moreover, immunostaining and reverse transcription-polymerase chain reaction analysis revealed that endothelin B receptor expression was induced in NCC-/melb4 cells following treatment with 1,25-dihydroxyvitamin D3. The induction of endothelin B receptor by 1,25-dihydroxyvitamin D3 was also demonstrated in neural crest cell primary cultures, but not in mature melanocytes. The expression of microphthalmia-associated transcription factor was induced in NCC-/melb4 cells treated with 1,25-dihydroxyvitamin D3 and endothelin 3, but not by 1,25-dihydroxyvitamin D3 alone, suggesting that endothelin 3 may stimulate the expression of the microphthalmia-associated transcription factor gene after binding to the endothelin B receptor induced by 1,25-dihydroxyvitamin D3. These findings suggest a regulatory role for vitamin D3 in melanocyte development and melanogenesis, and may also explain the working mechanism of vitamin D3 in the treatment of vitiligo.
authors.affiliation: Department of Dermatology, St Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Watabe
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Soma
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Ito
authors.forename: Shiho
authors.initials: S
authors.lastname: Ooka
authors.forename: Kayoko
authors.initials: K
authors.lastname: Ohsumi
authors.forename: Takako
authors.initials: T
authors.lastname: Baba
authors.forename: Tamihiro
authors.initials: T
authors.lastname: Kawakami
authors.forename: Eri
authors.initials: E
authors.lastname: Hosaka
authors.forename: Satoko
authors.initials: S
authors.lastname: Kimura
authors.forename: Masako
authors.initials: M
authors.lastname: Mizoguchi
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000235:genetics; D004295:Dihydroxyphenylalanine / Q000032:analysis; D019334:Endothelin-3 / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D008544:Melanocytes / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D020460:Melanosomes / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D051739:Microphthalmia-Associated Transcription Factor; D008854:Microscopy, Electron; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics*; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D014157:Transcription Factors
chemical_list: D002120:Calcium Channel Agonists; D004268:DNA-Binding Proteins; D019334:Endothelin-3; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014157:Transcription Factors; D004295:Dihydroxyphenylalanine; D002117:Calcitriol