MELANOCYTES AND MELANIN PIGMENTATION 569 .:. . ?•-%,, ..?:: •...•, •.•...." '...:'-- . ': Z-' ,. •.•: ,.:.: :..,-.. . .---%..) ........ .. •, "?f. •. ,....: ..... ::.'.. ?•.• •' ,:.,• :".'.:..,4 :- ..•*• •. •"•'C•. • ( f .*'%::: ':%. :• ...:: .'/"• ::. i .......:" ..e-, •q*, , ,2: .:: ., . '•* ' :½ *• .-i'" "' •. :-. . .- .,.% .., : :.% ' - • 2' . .. : .:... -• .... ., /.-:.. .• : .: . " *:.:,...... . "•h .. • *'" . .. ,: . :,Z:.. .* ,:: .- ½:, . . • :. . ..,: .. .4•'. *' "- d •" :.,....•½%.•...' ,. ..:**:.......' : : .? -"'•'. :, -:-? :s.: ..... •.. .... :. -- ,, .. ... : •.' .•...:•:%..,.:%,,.. Figure 3. Pigment cells in monolayer culture. In situ fixation glutaraldehydc and osmium. 21760X. Part of a pigmented cell showing melanosomes and prcmelanosomes with varying degree of melanization. p--prcmelanosome, m--melanosome, and N--nucleus much larger cell bodies and shorter processes, in contrast to the small cell body and long and slender processes of the younger melanocytes. They are enzymatically inactive, contain intracytoplasmic melanin granules and usually do not kave premdanosomes.

570 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS BIOSYNTHESIS OF MELANIN The Metabolic Unit of Melanin Formation Seiji et al. (12) hypothesized that the tyrosinase is synthesized in ribosomes and transferred via the endoplasmic reticulum to the Golgi area, where tyrosinase is separated into small units, each o[ which be- comes surrounded by a membranous envelope. Within each envelope, tyrosinase molecules become aligned in the ordered pattern, after which melanin synthesis begins and the particle is known as a premelanosome. As melanin gradually accumulates, the premelanosome is eventually transformed into a uniformly dense and structureless particle called melanosome. Seiji and Iwashita (13) found that an incorporation of Dopa-C TM occurred only in premelanosomes and concluded that pre- melansomes are the specific site of melanin formation. Since tyrosinase activity was found in premelanosomes, smooth surface membranes, rough surface membranes and ribosomes, the presence of tyrosinase activity is not necessarily correlated with melanin formation. Nakai and Shubik (14), using electronmicroscopic radioautography, observed that an ap- preciable amount of Dopa-C TM was incorporated with premelanosomes. On the other hand, Zelickson et al. (15), using similar techniques, demonstrated in S-91 mouse melanoma that initial melanin synthesis occurred predominantly in the endoplasmic reticulum and associated RNP particles. The label was located to a large extent at the level of ribosomes and ER. It was the authors' opinion that this label prob- ably represents an insoluble monomer before polymerization rather than melanin itself, with movement toward and 5nal polymerization occurring within the melanosome. MELANIN PIGMENTATION The capacity of a melanocyte to synthesize melanin is determined by its genetic make-up, which limits its range of pigmentary changes. Within this limit melanin pigmentation of skin varies with: 1. The number of active melanocytes. Either the change in the rate of tyrosinase synthesis or in the rate of melanosome production in the melanocyte can affect the degree of pigmentation. 2. The amount of melanin granules in epidermal cells (melanocytes and epithelial cells). 3. The number of melanin-containing cells in the dermis--Dermal melanocytes and melanophages (macrophages with phagocytosed mela- nin).