908 .JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS assimilation produces not only sufficient energy for the follicles to [unction but also essential substances [or the follicle to metabolize fatty acid, nucleic acid, and steroid hormones. Several enzyme activities of both the sheath and bulb portions of hair follicles at different stages of hair growth were assayed with the microenzyme assay methods developed by Lowry (18-20). Thin sec- tions (20-50 •) of skin biopsies were first freeze-dried and small hair fol- licle samples (0.5 to lvg) were dissected under the microscope. The en- zyme activities were assayed by highly sensitive fluorometric measure- ments (20) within the limits at which the reaction rates were directly pro- portional to the reaction time as well as to the amounts of enzymes (11). The enzyme activities in all of the ariagert phases thus far studied are about the same (Fig. 2). However, there are conspicuous differences be- ENZYME• AGE HEXOKINASE PHOSPHORYLASE TELOGEN ANAGEN 'Fl. Trl' ANAGEN • ANAGEN • G6P DH G3P OH LDH FUMARASE Figure 2. Enzyme activities at different stages of the hair cycle. Each enzyme activity in the upper sheath at telogen stage is arbitrarily taken as 100% (i.e., three bars indicate 300% increase). White bars represent enzyme activities in the external sheath and black bars those in the bulb portion (12). (G3PDH z glyceraldehyde-3-phosphate dehydrogenase LDH = lactate dehydrogenase)

HUMAN HAIR FOLLICLES 909 tween the activities of telogen and anagen follicles. In the telogen stage, the enzyme activities in the upper half of the follicle are similar to those in the lower half, whereas in growing hair follicles the bulb generally has more enzyme activities than the external sheath. This change in activity is most dramatic in glucose-6-phosphate dehydrogenase (G6PDH), a key enzyme of the pentose cycle, where the impressive increases during ana- gen concur with the data obtained in the glucose-14C experiment, i.e., they both confirm the active participation of the pentose cycle in grow- ing hair follicles. As the hair follicles developed, phosphorylase activity increased con- comitantly in the external sheath and decreased in the bulb. Glycogen concentrations were elevated correspondingly, i.e., the anagen sheath contained 2.8 g glycogen/100 g dry weight, the bulb 0.44 (21). Thus, an inverse relationship exists between glycogen metabolism and biological activity. Glycogen accumulates in skin when the metabolism is sup- pressed (22, 23). How the mechanism of glycogen accumulation func- tions physiologically in the external sheath is still unknown, but the search for the mechanism should provide an interesting model for under- standing the metabolic control system in vivo. TESTOSTERONE METABOLISM In Vitro IN HUMAN HAIR FOLLICLES Wotiz et al. (24) have shown that human skin can metabolize testos- terone efficiently in vitro. Recently, Gomez and Hsia (25) incubated human skin with testosterone-4-nC and identified by paper chroma- tography and thin-layer chromatography such metabolites as andro- stenedione, 5a-dihydrotestosterone, 5a-androstanedione, androsterone, and epiandrosterone. The presence of an active catabolic pathway clearly suggests the physiological significance of skin, one of the largest organs in the human body. In order to study the etiologic factors for common baldness, we are concerned with the metabolic (catabolic) capacity of human hair follicles but not of whole skin. The possi- bility has recently been considered that sebaceous glands may also con- tribute to testosterone metabolism in hair follicles however, it will not be discussed here. Recent evidence suggests that 5a-dihydrotestosterone rather than testosterone is the active androgen in the target tissue. Bruchovsky and Wilson (26-28), for example, clearly demonstrated that in the prostate the predominant androgen is not testosterone but 5a-dihydro- testosterone and that 5a-dihydrotestosterone retained in the nuclear