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Regulation of melanogenesis – controversies and new concepts
Author(s) -
Schallreuter Karin U.,
Kothari Sonal,
Chavan Bhaven,
Spencer Jennifer D.
Publication year - 2008
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2007.00675.x
Subject(s) - tyrosinase , tyrosine hydroxylase , transcription factor , microphthalmia associated transcription factor , chemistry , tyrosine , microbiology and biotechnology , melanin , biochemistry , intracellular , biology , enzyme , gene
Despite many efforts, regulation of skin and hair pigmentation is still not fully understood. This article focuses mainly on controversial aspects in pigment cell biology which have emerged over the last decade. The central role of tyrosinase as the key enzyme in initiation of melanogenesis has been closely associated with the 6BH 4 dependent phenylalanine hydroxylase (PAH) and tyrosine hydroxylase isoform I (THI) providing evidence for an old concept of the three enzyme theory in the initiation of the pigmentation process. In this context, it is noteworthy that intracellular L‐phenylalanine uptake and turnover to L‐tyrosine via PAH is vital for substrate supply of THI and tyrosinase. While PAH acts in the cytosol of melanocytes, THI and tyrosinase are sitting side by side in the melanosomal membrane. THI at low pH provides L‐3,4‐hydroxyphenylalanine L‐DOPA which in turn is required for activation of met‐tyrosinase. After an intramelanosomal pH change, possibly by the p‐protein, has taken place, tyrosinase is subject to control by 6/7BH 4 and the proopiomelanocortin (POMC) peptides α‐MSH melanocyte stimulating hormone and β‐MSH in a receptor independent manner. cAMP is required for the activation of microphthalmia‐associated transcription factor to induce expression of tyrosinase, for transcription of THI and for activation of PAH. The redundancy of the cAMP signal is discussed. Finally, we propose a novel mechanism involving H 2 O 2 in the regulation of tyrosinase via p53 through transcription of hepatocyte nuclear factor 1α which in turn can also affect the POMC response.