Melanogenesis — expanded notes
Melanocyte biology
Melanocytes are neural-crest-derived dendritic cells. In the epidermis, each melanocyte interacts with multiple keratinocytes, forming the epidermal melanin unit. Melanosomes mature within melanocyte dendrites and are transferred to keratinocytes, where pigment is positioned above the nucleus to reduce UV injury.
Biochemical pathway
Tyrosinase catalyses the conversion of tyrosine to DOPA and DOPAquinone. DOPAquinone is a branch point: in the presence of cysteine, pathways favour pheomelanin; in the absence of substantial cysteine and with appropriate enzyme activity, eumelanin is produced. MITF is a major transcriptional regulator of melanocyte differentiation and melanogenic enzymes.
UV response
UV exposure causes keratinocyte DNA damage and stimulates p53-dependent pro-opiomelanocortin expression. Alpha-MSH binds MC1R on melanocytes, increases cAMP and promotes MITF and tyrosinase activity. This produces delayed tanning. Immediate pigment darkening is largely due to oxidation and redistribution of existing pigment.
Factors affecting pigmentation
- Genetic variation in MC1R and other melanogenic genes affects eumelanin/pheomelanin balance.
- Hormonal influences, including pregnancy-related changes, can contribute to melasma.
- Inflammation can increase melanogenesis and cause pigment incontinence, leading to post-inflammatory hyperpigmentation.
- Some drugs and chemicals can cause pigmentation through melanin stimulation, drug deposition or post-inflammatory change.
Clinical assessment
Describe pigment colour, symmetry, border, distribution, relation to sun exposure and preceding inflammation. Brown pigment is often epidermal; slate-grey or blue-grey pigment may indicate dermal melanophages or deeper pigment. Wood lamp can help delineate some epidermal pigmentary changes but has limitations, particularly in darker phototypes.
Photoprotection
Melanin reduces but does not eliminate UV injury. Recommend shade, protective clothing and broad-spectrum sunscreen. Visible light may worsen melasma and post-inflammatory pigmentation; tinted formulations containing iron oxides can provide additional visible-light protection.