THE SKIN AS A COMMUNITY OF STRUCTURES The sulphur-containing amino acid, cystine, has been reported to form as much as 18 per cent of the dry, ash-free weight of human hai•. The protein associated with the melanin pigment has also been reported to contain cystine and methionine. A further link between the sulphm- containing amino acids and melanin formation lies in the reports of the association of lower concentrations of water-extractable materiMs containing thiol groups (-SH) in regions of excessive pigmentation compared with regions of normal or reduced pigmentation (Rothman et al., 1953). Further- more, thiol compounds, such as cysteine, are claimed to protect tissue from the effects of radiation. A solution of cysteine hydrochloride injected beneath the skin of the mouse gave marked protection against a dose of X-radiation which would have caused almost complete destruction of the melanocytes in the hair bulbs. Normal black fur grew from the irradiated area of the protected mice, whereas unprotected mice grew grey hair after receiving a similar dose of radiation (Kulwin, 1953). The action of cysteine in preventing those effects which probably arise from the reactivity of the free radicals produced by irradiation, the inverse correlation between concentration of thiol compounds and pigmentation of the skin, and the similarity of oxidised melanin pigments to that formed in kwashiorkor, give support to the suggestion that thiol compounds might act as regulators of the state of oxidation of the pigment. The importance of the sulphur-containing amino acids in both keratin and melanin formation is evident, but some doubt exists whether the relation to melanin is direct or whether it is through the interaction of sulphur compounds with another component of the system. Essential to both the formation of melanin and of keratin is an adequate supply of copper in the diet. Copper deficiency in the diet of sheep producing non- pigmented wools reveals itself in the appearance of straight, lustrous wool lacking the marked crimp of the normal fleece, and the wool fibres have a lower tensile strength. Histological examination shows that keratinisation in which the wool structure becomes stabilised in the conversion of combined cysteine to combined cystine takes place over a much greater length of the follicle and the wool may still be in a plastic condition at a distance almost two-thirds the way up the follicle. Keratinisation is normally completed at a level of less than one-third the distance up the follicle. Copper there- fore plays an important part in the oxidative process converting thiol to disulphide (Marston, 1946). The association of copper and melanin forma- tion has been shown by the loss of the ability to produce pigment in direct copper deficiency, and also when substances known to combine strongly with copper are present in the diet. Dark-coloured cattle grazed on areas of low copper content in the pasture undergo a marked greying of the hair, and black rats fed upon a copper-deficient diet show a similar change in coat colour. Rats fed phenylthiourea (phenylthiocarbamide), cysteine, thioura½il

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS or the dithiol, BAL, grew grey hair, but when these substances were omitted from the diet the hair growing subsequently was of the normal black colour. These substances form very stable co-ordination compounds with copper ions and reduce their availability to other systems such as those involved in pigmentation. Similar effects have been noted in human subjects, prolonged treatment with BAL producing grey hair in one case and thiouracil produced areas of depigmentation in a Negro subject (Lerner and Fitzpatrick, 1953). Copper is now known to be an essential part ol the enzyme tyrosinase which as stated above plays a major part in melanin formation, and it is possible that the effects of sulphur-containing compounds in the normal skin mediated through their control of the amount of coppe• available to enzymes. Zinc is another metal required for the formation of normal melanin and keratin, •nd rats fed a diet deficient in this metal grew fur which was soft and woolly, and the portions of fur normally black were light grey in colour (Stirn et al., 1935). Zinc ions are necessary for the activity of certain enzymes so that control of the availability of zinc by thiol compounds might also control the activity of such enzymes. The process of keratinisation with the conversion of thiol groups to disulphide groups occurs in a region of the hair follicle, the keratogenous zone, above the hair bulb. Histological procedures reveal a high concentra- tion of thiol groups in this region, but in the bulb itself the concentration is much lower. The thiol groups, if present as such in the bulb, are screened in some way, and melanin formation which is influenced by the concentration water-soluble thiol compounds proceeds readily. The state of the thiol groups in the hair bulb is not known: they may be held within a protein inaccessible to chemical reaction and become available only as a process akin to denaturing of the protein takes place. SUMMARY The cells responsible for the pigmentation of the skin and hair are of nervous origin, and their particular products which are probably related to a nervous function have become utilised to form melanin. The distinction between these cells and those of epidermal origin which produce keratin is reflected in the distinctive response of the melanocytes to certain conditions which appear to have little effect on keratin formation. These two types of cells, however, have a number of links in common, of which the relations to sulphur-containing compounds and the metals, copper and zinc, have been discussed. There appears some evidence of a system of inter-regulation with the availability of the metals to enzymes being controlled by the sulphur compounds. The metals might also displace each other in various systems and have effects as oxidising catalysts on the sulphur compounds. 284