MUCOPOLYSACCHARIDES IN HUMAN EPIDERMIS 157 However, at present there is no evidence that mucopolysaccharides per- form such functions in the horny layer our own preliminary experiments have not yielded conclusive data. A much more likely role has been suggested by Sylvgn (19). He noted that metachromasia in the rat skin fluctuated with the skin cycle. The greatest concentrations occurred during periods of intensive growth, the lowest amounts in the resting stage. Sylvgn believed that the metachro- matic substance may act as a sulfate donor and help in building keratinous material. Recently, this theory received further support when it was found that sheep could synthesize cystine in the hair follicles from sulfate (20). In rat follicles the uptake of labeled sulfate coincided with metachromasia (21). None of these studies conclusively prove that mucopolysaccharides are essential for the synthesis of keratin. However, in the past few years evidence has also been obtained from clinical observations of hair loss in which a disturbed mucopolysaccharide metabolism may play a role. HAIR Loss AND MUCOPOLYSACCHARIDES There are three recently discovered types of hair loss which may be caused by anomalous mucopolysaccharide metabolism. Two of these conditions, baldness in hypervitaminosis A and from anticoagulants, are man-made, iatrogenic the third, alopecia mucinosa, is of unknown origin. 1. •11opecia frorn Chronic l•itamin oentoxication About half of the patients suffering from the effects of prolonged excessive intake of vitamin A, lost their hair to varying extents (22). The hair loss was always reversible after discontinuation of vitamin A. Unfortunately, in these cases no histochemical studies for mucous material have been car- ried out not even biopsies were performed, and therefore the histologic features of this condition are unknown. Nevertheless, it is not far-fetched to assume that a disturbance in the hypothetical mucopolysaccharide- keratin metabolic chain may be responsible for this hair loss. In tissue cultures excess vitamin A causes mucinous transformation of the keratiniz- ing cells of the chick epidermis as shown in the classic studies of Fell and Mellanby (23) and confirmed by Weiss and James (24) and by Lasnitzki and Greenerg (24a). Local application of excessive vitamin A to the rat skin also induces changes suggestive of mucinous degeneration (25). Vitamin A also increases the uptake of sulfur from labeled sulfate in the mucopolysaccharides of rat skin (26) and in rabbit hair (27). 2. •llopecia from Heparin and Heparinoids Administration of heparin and of a variety of synthetic anticoagulants leads to reversible hair loss in a high percentage of cases (28, 29 30). All these compounds are sulfated derivatives of various polysaccharides.

158 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Again the hair loss is reversible. The histologic and histochemical features of these conditions are unknown. The most likely assumption is that these anticoagulants act as competitive inhibitors of the natural mucopolysac- charides, thus preventing the synthesis of keratin. 3. •llopecia mucinosa This rare type of hair loss was discovered by Pinkus in 1957 (31). It is characterized by the accumulation of mucous material in the hair follicles and sebaceous glands. Under the name "mucophanerosis seboglandularis et intrafollicularis," it was later described by Braun-Falco (32) who dis- tinguished two varieties the "idiopathic" kind (i.e. of unknown origin) and a type associated with various other skin diseases. In summary, there is strong evidence in favor of the assumption that mucopolysaccharides are essential for the synthesis of keratin. It is premature to decide whether they act as "building stones, .... precursors" or as "donors of active sulfur" (33). SUMMA RY Mucopolysaccharides occur in a variety of epidermal structures, especi- ally during intense proliferation. Their presence has been demonstrated with histochemical and direct chemical methods. Experimental and clin- ical studies indicate that these compounds are probably essential for the synthesis of normal keratin. Hair loss from excessive intake of vitamin A, from heparin and heparinoids and in the condition called alopecia mucinosa, may be due to disturbances in the hypothetical mucopolysaccharide-ker.atin metabolic chain. ztcknow/edgment: The assistance of the Chesebrough-Pond's Inc. is gratefully acknowledged. ADDENDUM After completion of this manuscript, Hirsch and Helwig presented his- tochemical and physicochemical studies on an epidermal tumor, called syringochondroma, where the epidermal cells produce a metachromatic material which is transformed into cartilage (z/re. ztcad. DermatoL, Dec., 1958). Our own recent work suggests that in pathologic horny layers a highly resistant mucopolysaccharide complex is retained in the scales. REFERENCES (1) Flesch, P., 7. Invest. Dermato/., 31, 63 (1958). (2) Rothman, S., "Handbuch d. Haut-u. Geschlechtskrkh.," Vol. I./2 Berlin, Julius Springer Publisher (1929), pp. 162-163. (3) Wislocki, G. B., Bunting, H., and Dempsey, E. W., vim. 5 t. vinat., 81, 1 (1947). (4) Braun-Falco, O., virch. Dermatol. u. Syphilis, 198, 111 (1954). (5) Sylvan, B., and Mahngreen, H., Lab. 2rnvest., 1,413 (1952). (6) Holmgren, Hi., yahrb. Morphol. rnikroskop. vinat., 47, 489 (1940). (7) Sylvgn, B., Klin. F•ochschr., 17, 154 (1938).