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Up‐regulation of melanin synthesis by the antidepressant fluoxetine
Author(s) -
Liao Sha,
Shang Jing,
Tian Xiaoli,
Fan Xueqi,
Shi Xiupu,
Pei Siran,
Wang Qian,
Yu Boyang
Publication year - 2012
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.1600-0625.2012.01531.x
Subject(s) - microphthalmia associated transcription factor , fluoxetine , melanin , serotonin reuptake inhibitor , tyrosinase , serotonin , antidepressant , chemistry , pharmacology , hypopigmentation , tranylcypromine , endocrinology , biology , receptor , biochemistry , enzyme , genetics , monoamine oxidase , hippocampus
Fluoxetine, a member of the class of selective serotonin reuptake inhibitors, is a potent antidepressant commonly used in clinical practice. Here, we report that fluoxetine increases cellular tyrosinase ( TYR ) activity, enhances the protein levels of microphthalmia‐associated transcription factor ( MITF ), TYR and tyrosinase‐related protein‐1 ( TRP ‐1) and eventually leads to a dramatic increase in melanin production in both murine B 16 F 10 melanoma cells and normal human melanocytes ( NHMC s). In well‐characterized C 57 BL /6 mouse models, systemic application of fluoxetine increased hair pigmentation by up‐regulating hair follicular MITF , TYR , TRP ‐1 and tyrosinase‐related protein‐2 ( TRP ‐2) protein levels. Using a serotonin 1 A receptor ( SR 1 A ) antagonist and RNA interference ( RNA i) technique, we revealed that SR 1A appears to be one of the involved pathways in the fluoxetine‐induced melanogenesis in B16F10 cells. These results suggest that fluoxetine may hold a significant therapeutic potential for treating skin hypopigmentation disorders, and SR 1A may serve as a novel target in modulating melanogenesis.