912 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS ,u ,u mole/lOOmg/hr 26,000 24,000 22,000 20,000 18,000 16,000 14,000 12,000 io,00o 8,000 6,000 4,000 2,000 AO AO AD AD 0 D GROWING GROWING GROWING GROWING (Z) (2) (5) Figure 4. 5a-Reductase activities of growing and resting hair follicles. Average of (n) experiments. Abbreviations same as for Fig. 3 resting hair follicles the rate of active androgen formation is greatly increased by addition of the colactor, TPNH. These data, therefore, suggest that the growing hair follicle can generate sufficient TPNH from a carbon source while resting follicle cannot hence the endog- enous level of TPNH in the resting follicles is the limiting factor. As indicated in the preceding section, the most remarkable metabolic shift occurring during the transformation from the resting to the grow- ing hair follicles is the marked increase in the cytoplasmic TPNH level (Table V). Ultramicromeasurements of pyridine nucleotides by the cycling technique (31) a•ee with our previous calculation of the Table VI Analysis of Human Hair Follicles (Bulb Portion) for Pyridine Nucleotides by the Cycling Technique" Growing Resting TPN + 38 32 TPNH 89 53 DPN + 394 240 DPNH 644 377 "Results represent means of 5 determinations, expressed as tztzmoles/mg dry weight. (TPN + triphosphopyridine nucleotide DPN + = diphosphopyridine nucleotide TPNH and DPNH reduced TPN and DPN).

HUMAN HAIR FOLLICLES 913 0 epiondrosterone Figure 5. Prcsumcd pathways of testosterone metabolism in hair follicles balance (Table VI). Thus, these data suggest that mainly growing hair follicles are affected by the tissue-active androgen whereas the resting follicles catabolize testosterone to androstenedione which is a relatively inactive androgen. In Fig. 5, the different pathways of testosterone in hair follicles are summarized. Only traces of epiandro- sterone, androsterone, and androstanediol were detectable when testos- terone was used as the substrate. Normal skin does not produce 5•-metabolites (25). In addition to the increase in pentose cycle activity, we must con- sider the possible increase in TPNH generating systems (such as the isocitrate dehydrogenase and •nalic dehydrogenase reactions in the grow- ing hair follicles) that increase synthesis of the active form of the hormone from testosterone.* Further experimental evidence is required to de- termine whether these speculations are correct. At present, we have solid proof only that human hair follicles actively metabolize testosterone in vitro with a major product being androstenedione, that they can pro- duce 5a-dihydrotestosterone at a rate comparable to that of the prostate, and that they contain sufficient 5a-reductase activity to account for the formation of this tissue-active androgen. * We are unable to dctect transdehydrogcnasc activity in human hair follicles. Therefore, the balance of pyridine nucleotides should be kept shifting to an excess of TPNH. Unpub- lished observation by K. Adachi.