Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 13.09.2021

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melanogenesis; Melanogenesis

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Melanins (from Greek melas = black, dark) are brown or black pigments (dyes) which are produced by the enzymatic oxidation of tyrosine (enzymatic browning). In humans they cause pigmentation, i.e. the colouring of skin, hair or eyes. Melanins are mainly found in vertebrates and insects, as a dye in the ink of squid and very rarely in microorganisms and plants. The melanin content in the individual skin types varies considerably between 17.9 and 72.3%.

General information
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In vertebrates, melanin is formed in the melanocytes of the skin and in the retina of the eye. Melanin significantly determines skin and hair colour as well as the individual risk of melanoma. It occurs in humans in two main variants:

  • brown/blackish (eumelanin)
  • Light yellowish (pheomelanin).

However, there are also other coloured, chemically well defined variants (trichromes).

The extent of melanin synthesis is determined by the gene for melanocortin receptor 1 (MC1R). In humans, MC1R is encoded on chromosome 16, gene locus q24.3.

For the melanin synthesis 3 key enzymes are important:

Tyrosinase is the key enzyme in melanin production. It catalyses two different reactions. First it converts tyrosine into dopa and then dopa into DOP-quinone. The melanin synthesis rate is largely controlled by systems that regulate the production and activity of tyrosinase. The synthesis process takes place in the rough endoplasmic reticulum and in the Golgi apparatus of melanocytes. DOPAquinone is oxidized and polymerized to phaeomelanin.

DOPAchrome automerase (DCT) is an enzyme that converts DOPAchrome into DHI-2-carboxylic acid (DHI-carboxylic-acid = DHICA), which forms another type of melanin, the light brown DIICA-melanin.

Tyrosinase-related protein-1 ( TYRP1) is an enzyme crucial for the transport of tyrosine to the melanosomes

After synthesis, melanin is stored in intracellular granules called melanosomes. The size of these granules varies depending on the pigmentation type. The darker the skin is pigmented, the larger they are.

The maturation of melanosomes takes place in the melanocytes in 4 stages. For the transformation of stage I melanosomes into stage II melanosomes, the structural protein MART1 is absolutely necessary.

Melanin is formed in the skin in increased quantities under the influence of sunlight (see chromophores below) and serves as light protection against the harmful influence of UV radiation. Furthermore, the proliferation and differentiation of melanocytes and thus of melanin is increased by growth factors which are formed by keratinocytes and fibroblasts of the skin. Antagonistically, the thick head 1 protein (DKK-1) acts via the WNT/beta-catein signaling pathway (see below catenins), which is produced in large quantities in the fibroblasts of the palms.

The pigment phenotype itself is subject to a complex genetic programme. Essentially, pigmentation is controlled by the melanocortin 1 receptor (MC1R) gene, which in turn encodes MC1R, a receptor coupled to a G protein (guanine nucleotide-binding proteins) on the surface of melanocytes. MC1-R is regulated on the one hand by the stimulating pituitary hormones melanocyte-stimulating horm one (MSH), beta-lipotropin and ACTH, which in turn are produced from the precursor hormone proopiomelanocortin - Clark AJ (2016), and on the other hand in an antagonistic way by the agouti-signalling protein.

The synthesis of melanin can be disturbed by genetic predisposition or by genetic damage acquired over time. If production is blocked, the dyes in the skin and eyes are also missing, which can lead to different types of pigment defects (see depigmentation below). An analogously induced overproduction of melanin leads to the pathological condition of hyperpigmentation.

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The antidiabetic drug metformin inhibits melanogenesis in vitro as well as in vivo (by down-regulation of cAMP). The investigations suggest that metformin can also be used in the topical treatment of hyperpigmentation.

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  1. Brenner M et al (2010) Basics of skin pigmentation. Dermatologist 61: 554-560
  2. Clark AJ (2016) 60 YEARS OF POMC: The proopiomelanocortin gene: discovery, deletion and disease. J mol endocrinol 56:T27-37.

  3. Giehl K et al (2010) Genetically caused pigmentation disorders. Dermatologist 61: 567-577
  4. Lehraiki A et al (2014) Inhibition of melanogenesis by the antidiabetic metformin.
    J Invest Dermatol 134:2589-2597


Last updated on: 13.09.2021