914 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS ENZYMATIC BASIS FOR HORMONAL CONTROL OF HAIR FOLLICLE METABOLISSI One o[ the most significant biological contributions in the last decade is the discovery ot adenosine-3', 5'-cyclic-monophosphate (cyclic AMP) as a common mediator for different hormones working at their re- spective target tissues (32, 33). For example, the action of adrenocortico- tropic hormone (ACTH) on adrenal cortex, and of thyroid-stimulating hormone on thyroid gland, causes the same intracellular response in their respective tissues--a rapid increase in cyclic AMP. This increase in cyclic AMP influences a variety ot biochemical processes, such as increases in glucose oxidation, lipolysis, steroidogenesis, etc. The intracellular con- centration of cyclic AMP is regulated by the synthetic enzyme, adenyl cyclase, and the degradative enzyme, a specific phosphodiesterase. Nearly all hormones stimulate adenyl cyclase rather than inhibit phosphodiester- ase, with a subsequent increase in the intracellular level ot cyclic AMP (32,33). Notwithstanding the rapid accumulation ot literature on the role ot adenyl cyclase and cyclic AMP in the past five years, the existence ot this important mediator has not been reported in skin and its append- ages. Accordingly, we began to test the hypothesis that human scalp hair tollicles, particularly those ot the male, must contain adenyl cyclase, the activity ot which must be influenced by the tissue-active sex hormones. Preliminary data thus far obtained indicate that our assump- tion is correct.* To prepare crude adenyl cyclase, [Tesh hair follicles were obtained by plucking 50 to 100 gTowing scalp hairs, and homogenizing them in a medium consisting of 0.25M sucrose, lmM EDTA, lmM MgCI_% and 0.2M tris-HC1 buffer, pH 7.4. The homogenate was centrituged at 12,000 g for 10 rain at 4øC. The precipitate was washed twice with 0.25M sucrose and resuspended with appropriate amounts of water. Five •1 of an assay reagent mixture, slightly modified from that of Krishna (34), (e.g., 10 times increased amounts of ATP-•4C), were added to 5 •1 of this crude particulate preparation. This mixture was incubated for 3 hours at 37øC with and without additions of sex hormones. The resulting cyclic AMP was isolated by thin-layer chro- matography as described by Tao and Lipmann (35). * To be reported elsewhere in detail by K. Adachi and M. Kano.

HUMAN HAIR FOLLICLES 915 Table VII Adenyl Cyclase Activity of Growing Hair Follicles Subjects #KA #AD #KO Additions (• (m•moles/hr/mg wet wt tissue) Av. None (control) 68.8 64.8 68.0 67.2 4- Testosterone 68.8 40.0 76.0 61.6 4- 5a-dihydrotestosterone 28.8 16.0 52.0 32.3 4- Esterone 150.0 ... 141.5 145.8 The concentration of each hormone added was 50/•g/ml reagent mixture. As shown in Table VII, the particulate fraction obtained froxn scalp hair follicles no doubt possesses sex hormone dependent adenyl cyclase activity. A male sex hormone (if it is tissue active) inhibits the adenyl cyclase whereas a female hormone increases its activity. The inhibition of this enzyme by 5oz-dihydrotestosterone but not by testosterone suggests strongly that the former is the tissue-active male hormone in hair follicles. Thus, data presented in Table VII represent the enzymatic evidence for the hormonal control of hair follicle metabo- lism. * STUDIES ON THE STUMP-TAILED MACAQUE--MODEL SYSTEM FOR COMMON BALDNESS Montagna (6-8) discovered that some subhuman prixnates develop baldness, a condition long considered peculiar to the human scalp. Of particular interest are the stmnp-tailed xnacaque, orangutah, and chixn- panzee, many of whom reveal during maturation varying degrees of alopecia in a triangular area just above the eyebrows. Since the stump- tailed macaque is a more practical laboratory animal than the others, it was selected for these studies on common baldness. To understand the difference between the bald and the hairy scalp, one must understand the structure and distribution of hair follicles in the scalp. The "hairy" part contains mostly large, stout, terminal ariagert hairs while the bald region contains thin, small, veilus-type ariagert and telogen hairs (Fig. 6). A detailed trichograxn study on the scalp hair follicles of the stuxnp-tailed macaque revealed (36) that both the hairy and the bald scalp contained about the same number of hair *• Both dihydrotestosterone and esterone show no effect on cyclic AMP phosphodiesterase activities in the hair follicles (unpublished observation).