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Melanin production occurs inside the melanosomes located in the melanocytes. The process of melanin synthesis begins with the hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine (DOPA) using the enzyme tyrosinase (Figure 33-1).1 Two types of melanin are produced: eumelanin and pheomelanin. The relative amounts of these two forms of melanin determine hair color and skin tone. Individuals with darker skin tones have mostly eumelanin and a lower level of pheomelanin, while the opposite is true in people with a light skin color.


The conversion of tyrosine to melanin is controlled by the rate-limiting enzyme tyrosinase.

Tyrosinase is the rate-limiting enzyme for melanin production. Tyrosinase is stimulated by ultraviolet (UV) radiation, DNA fragments such as thymidine dinucleotides that emerge as a result of UV exposure,2 melanocyte-stimulating hormone (MSH), and growth factors such as bFGF and endothelin. Protein kinase C3,4 and the cyclic adenosine monophosphate (cAMP)±protein kinase A pathway2 play a role in increasing melanin production as do prostaglandins (D2, E2, and F2), tumor necrosis factor-α (TNF-α), and interleukins (IL-α, IL-1β, and IL-6).2–5 Vitamin D3 may play a role in stimulating melanogenesis as well.6 For more information, please see Chapter 13 of Cosmetic Dermatology: Principles and Practice, 2nd edition (McGraw-Hill 2009).

The most popular way to treat unwanted skin pigmentation is through the use of tyrosinase inhibitors. These do not eliminate melanin that is already present but help prevent future melanin production in the treated area. It is usually necessary to wait 8 to 16 weeks to see improvement in pigmentation. Tyrosinase inhibitors covered in this section include: aloesin, arbutin, hydroquinone, kojic acid, mulberry extract, vitamin C (ascorbic acid), and cucumber.


1. +
Park  HY, Yaar  M. Disorders of melanocytes. In: Goldsmith  LA, Katz  SI, Gilchrest  BA,  et al. eds. Fitzpatrick’s Dermatology in General Medicine. 8th ed. New York: McGraw-Hill; 2012:773–774.
2. +
Khlgatian  MK, Hadshiew  IM, Asawanonda  P,  et al. Tyrosinase gene expression is regulated by p53. J Invest Dermatol. 2002;118:126.  [PubMed: 11851885]
3. +
Chang  MW. Disorders of hyperpigmentation. In: Bolognia  JL, Jorizzo  JL, Schaffer  JV, eds. Dermatology. 3rd ed. London: Saunders; 2012:1051.
4. +
Park  HY, Russakovsky  V, Ohno  S,  et al. The beta isoform of protein kinase C stimulates human melanogenesis by activating tyrosinase in pigment cells. J Biol Chem. 1993;268:11742.  [PubMed: 7685020]
5. +
Lee  JH, Park  JG, Lim  SH,  et al. Localized intradermal microinjection of tranexamic acid for treatment of melasma in Asian patients: A preliminary clinical trial. Dermatol Surg. 2006;32:626.  [PubMed: 16706756]
6. +
Tomita  Y, Torinuki  W, Tagami  H. Stimulation of human melanocytes by vitamin D3 possibly mediates skin pigmentation after sun exposure. J Invest ...

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