Melanogenesis: The Physiology of the Pigmentary System.

Melanogenesis describes the complex and essential process of pigment synthesis by which melanin is produced and distributed by melanosomes in the epidermis or hair follicles. This pigment, generally black or brown, determines the color of skin, hair, and the iris of the eye.

Melanin is synthesized inside special organelles, the melanosomes, which are themselves contained within melanocytes, globular cells with numerous cellular extensions (melanocyte dendrites) that enable them to make contact with several keratinocytes up to the spinous layer (one of the layers of the epidermis). They are established at the dermal-epidermal junction, which rests on the epidermal basement membrane. The number of melanocytes varies according to the area of the body: we count around 1,000 to 1,5000 per mm2 on the body, and 2,000 or more per mm2 on the face.

Melanin is produced through a cascade of reactions:

1. Synthesis of enzymes required for this mechanism: Among the enzymes involved in this process are tyrosinase, tyrosinase-related proteins-1 (TRP-1) and tyrosinase-related proteins-2 (TRP-2). These are proteins capable of triggering, activating and regulating the various chemical reactions leading to the synthesis of melanin pigments. They are synthesized in the rough endoplasmic reticulum (REG), then delivered to the Golgi apparatus via vesicles;

2. Melanosome formation: Melanosomes are cytoplasmic organelles containing the enzymes formed in the previous stage. They are formed by the fusion of microvesicles. At this stage in the pigmentary system melanosomes are still unpigmented (immature) and tyrosinases are inactive;

3. Melanin synthesis: Melanin is produced by the enzymatic transformation of tyrosine, an amino acid supplied by the bloodstream, under the action of tyrosinase. Following minor divergences in the synthesis pathway, two types of melanin pigments can be produced: eumelanins (or granular pigments) of the black to brown type, and pheomelanins (or diffuse pigments) of the yellow to reddish-brown type, with the intervention of sulfur compounds (either in the form of an amino acid, cysteine, or in the form of a tripeptide, glutathione);

   Note: In light skins, melanosomes are few 

   and often incompletely matured, 

   as well as being rapidly degraded, 

   making the skin less photo-protected and 

   therefore more exposed to solar damage 

   (sunburn), whereas in dark skins, 

   they are numerous and mature.

4. Transfer of melanosomes from melanocytes to keratinocytes: Many melanosomes migrate from the cell body, where they are produced, to the tips of melanocyte dendrites, where they accumulate, before being transferred to the surrounding keratinocytes in the upper layers of the epidermis to ensure epidermal pigmentation and photoprotection against UV rays. Each melanocyte is in contact with around 36 keratinocytes to which melanosomes migrate;

5. Melanosome degradation in keratinocytes: Once transferred to adjacent epidermal cells, melanosomes are then progressively eliminated with the keratinocytes as they ascend towards the skin surface.

Note: Differences in skin pigmentation 

are due to the proportion of each type of melanin 

synthesized and the size of melanosomes 

(i.e., the quantity of melanin), and not the 

numbers of melanocytes, which remain 

roughly equivalent for different skin tones.