Melanogenesis

Melanogenesis is the biological process by which melanin pigment is produced in specialized pigment cells called melanocytes, primarily located in the epidermis and hair follicles. The pigment determines skin, hair, and eye coloration and contributes to protection against ultraviolet (UV) radiation.

The core biochemical pathway centers on the enzyme tyrosinase, which initiates melanin synthesis from the amino acid tyrosine. Tyrosinase converts tyrosine to DOPA and then to DOPAquinone, after which additional reactions mediated by tyrosinase-related proteins TYRP1 and TYRP2 shape the final pigment. The pathway can yield two main types of melanin: eumelanin, which is brown to black, and pheomelanin, which is red to yellow. The balance between these pigments is influenced by genetic and environmental factors, particularly signaling through the melanocortin 1 receptor (MC1R) and the transcription factor MITF, which regulates the expression of TYR, TYRP1, and TYRP2.

Regulation of melanogenesis involves multiple signaling pathways. Ultraviolet (UV) exposure increases melanin production via a p53-mediated cascade that leads to increased secretion of α-melanocyte-stimulating hormone (α-MSH), activating the cAMP–PKA–CREB pathway and upregulating MITF. Melanosome production and maturation occur within melanocytes, and mature melanosomes are transported to the cell periphery by motor proteins such as Rab27a and myosin Va, then transferred to keratinocytes. In keratinocytes, melanosomes form a protective cap over the nucleus, helping shield DNA from UV damage.

Variations in pigmentation arise from genetics, hormonal influences, and environmental factors. Clinically, hypopigmentation disorders (e.g., albinism) and hyperpigmentation disorders (e.g., melasma) reflect disruptions in melanogenesis or melanosome transfer.