Melanogenesis: Everything you need to know about the physiology of the pigmentation system.

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

Melanins are synthesized within specific organelles, the melanosomes, which are themselves contained within melanocytes, these are globular-shaped cells equipped with numerous cellular extensions (melanocyte dendrites) that allow them to interact with several keratinocytes, extending up to the spinous layer (one of the layers of the epidermis). They are located at the dermo-epidermal junction which rests on the basal membrane of the epidermis. The number of melanocytes varies depending on the regions of the body: we count approximately 1,000 to 1,500 per mm2 on the body and 2,000 or more per mm2 on the face.

Melanin is produced as a result of a cascade of reactions:

1. Synthesis of enzymes necessary for this mechanism : Among the enzymes involved in this process, we have tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-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 at the level of the rough endoplasmic reticulum (RER), and then transported to the Golgi apparatus via vesicles;

2. Melanosome Formation : Melanosomes are cytoplasmic organelles within which the enzymes formed in the previous step are contained. They are formed by the fusion of micro-vesicles. At this stage, the melanosomes are still non-pigmented (immature) and the tyrosinases are inactive;

3. Melanin Synthesis : Melanin originates from 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: the eumelanins (or granular pigments) ranging from black to brown and the pheomelanins (or diffuse pigments) ranging from yellow to reddish-brown with the involvement of sulfur compounds (either in the form of an amino acid, cysteine, or in the form of a tripeptide, glutathione);

   Note : In fair skin, melanosomes are few in number and often incompletely matured, in addition to being rapidly degraded, making the skin less photo-protected and therefore more exposed to sun damage (burns, sunburns...), whereas in dark skin, they are numerous and mature.

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

5. Degradation of melanosomes in keratinocytes: Once the transfer to adjacent epidermal cells is completed, the melanosomes are then gradually eliminated with the keratinocytes as they ascend to the skin surface.

Note : The differences in skin pigmentation are due to the proportion of each type of melanin synthesized and the size of the melanosomes (thus the amount of melanin), not the number of melanocytes, which remain substantially equivalent across different skin tones.