Melanogenesis
The biological process by which melanocytes produce melanin pigment. Melanogenesis is initiated when alpha-MSH binds MC1R on melanocytes, activating tyrosinase. Afamelanotide is a synthetic alpha-MSH analogue that stimulates melanin production for photoprotection in erythropoietic protoporphyria.
Technical Context
Melanogenesis pathway: α-MSH binds MC1R on melanocytes → Gαs activation → adenylyl cyclase → cAMP → PKA → CREB phosphorylation → MITF (microphthalmia-associated transcription factor) upregulation → increased transcription of melanogenic enzymes: tyrosinase (rate-limiting enzyme converting tyrosine → DOPA → dopaquinone), TRP-1 (tyrosinase-related protein 1), and TRP-2/DCT (dopachrome tautomerase). Dopaquinone branches into eumelanin pathway (brown-black, photoprotective — via DHI and DHICA intermediates) or pheomelanin pathway (red-yellow, less protective — via cysteinyl-DOPA when cysteine is available). Afamelanotide ([Nle4, D-Phe7]-α-MSH) has approximately 100-1000× the potency of native α-MSH at MC1R, preferentially stimulating eumelanin production. The resulting increased eumelanin absorbs UV radiation and dissipates it as heat, providing photoprotection that benefits EPP patients by reducing protoporphyrin-mediated phototoxic reactions.