XI International Pigment Cell Conference

Pheomelanin is synthesized within melanocytes of hair follicles in mice of appropriate Agouti (a)or Extension (e)locus genic constitution. Alleles at the a-locus program pheomelanogenesis by altering the internal environment of hair follicles whereas alleles at the e locus do so by direct action through the genome of the melanocyte. For example, although transplanted recessive yellow (ele) melanoblasts synthesize pheomelanin within "eumelanic (a/a, B/B,E /E ) hair follicles," dominant (Ay/-) lethal yellow melanocytes produce eumelanin. Injections'of melanocyte-stimulating hormone induce pheomelanic follicular melanocytes of AY/mice, but not those of ele mice, to switch to eumelanin synthesis. Although it is generally maintained that pheomelanin synthesis is restricted to follicular melanocytes in mice, similarities between the ultrastructure of epidermal and follicular melanocytes in recessive yellow mice question this interpretation. A follicular melanocyte in agouti (A/A) hair follicles synthesizes both pheomelanosomes and eumelanosomes. Apparently, both types of melanosomes derive from a common multivesicular body-like structure which contains filaments as well as microvesicles. Filaments become the major component of the internal matrix in eumelanosomes whereas microvesicles predominate in pheomelanosomes. Microvesicles may serve to transport tyrosinase from the GERL/GOLGI complex where it has undergone glycosylation and, possibly, to isolate tyrosinase from inhibitory melanogenic substrates such as cysteine within the melanosome. Compared to eumelanocytes, tyrosinase activity is reduced in pheomelanocytes and its electrophoretic profile altered. At present little is known about how genes trigger pheomelanin synthesis and the extent to which the type of melanin synthesized influences melanosome morphology. The literature available suggests a tentative model for discussion.