Abstract
Finasteride is a well-known 5α-reductase inhibitor used for treatment of alopecia and prostate cancer. But the effect of finasteride in regulating melanogenesis is still unclear. In the present study the role of finasteride on melanogenesis was investigated. Finasteride decrease melanin level in melanocyte melan-a cells and B16F10 melanoma cells without inducing cytotoxicity. MC1R (melanocortin 1 receptor) protein expression was also inhibited by finasteride thereby decreasing the expression of adenylate cyclase, MITF (Melanogenesis associated transcription factor), tyrosinases, TRP (tyrosinase-related protein) -1 and -2. Thus our study suggest that finasteride inhibits melanogenesis in melanocyte and melanoma cells by inhibiting MC1R.
Highlights
Melanocytes are specialized skin cells that determine hair and skin color through the production of pigments called melanin
Melanocyte growth medium with supplements was purchased from Promo Cell (Heidelberg, Germany). 12-O-tetradecanoylphorbol-13-acetate (TPA), 1-phenyl-2thiourea (PTU), kojic acid, Triton X-100, phenylmethylsulfonyl fluoride (PMSF), aprotinin, mushroom tyrosinase, 3,4-dihydroxy-L-phenylalanine (L-DOPA), a-MSH, DMSO, and finasteride were purchased from Sigma-Aldrich (St.Louis, MO, USA). b-defensin-3 was purchased from Prospec (East Brunswick, NJ, USA)
Since finasteride treatment resulted in a decrease of MITF expression (Fig. 3) which is known to be driven by adenylate cyclase, we investigated the effect of finasteride on the protein expression of adenylate cyclase in melanocytes
Summary
Melanocytes are specialized skin cells that determine hair and skin color through the production of pigments called melanin. A-melanocyte-stimulating hormone (aMSH), derived from pro-opiomelanocortin (POMC), significantly enhances the activity of tyrosinase, the main enzyme regulating melanin synthesis. A-MSH activates the production of melanin by binding to the melanocortin1receptor (MC1R) on the cell membrane (Robbins et al 1993). Activation of MC1R induces adenylate cyclase and increases cAMP levels, thereby enhancing the expression of MITF (Melanogenesis associated transcription factor), a transcription factor that regulates protein kinase A (PKA) expression. MITF enhances melanogenesis by stimulating the transcription of tyrosinase and tyrosinase-related protein (TRP)-1 and -2 (Dessinioti et al 2011; Wolnicka-Glubisz et al 2014)
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