F2 ASSESSMENT OF POTENTIAL REGULATORS OF HAIR FOLLICLE-SPECIFIC PIGMENTATION
Kauser S1, Rothe H2, Noser F3, Tobin DJ1
1Medical Biosciences, School of Life Sciences, University of Bradford, United Kingdom
2Wella AG, Darmstadt, Germany
3Cosmital SA, Marly, Switzerland

While hair follicle melanocytes (HFM) and epidermal melanocytes (EM) share the same developmental origin in the neural crest, these sup-populations thereafter diverge in important ways in adult skin. However, by far the most striking difference between these two melanocyte sub-populations is the observation that the activity of the hair bulb melanocyte is under cyclical control, while epidermal melanogenesis by contrast appears to be continuous. Moreover, it is of note that vitiligo preferentially targets EM while alopecia areata targets HFM. So far we have been unable to specifically target these melanocyte sub-populations, such that the type or level of melanin may be modulated differentially in either epidermis or hair. The current study was designed to evaluate whether test compounds could target specific proteins/enzymes with resultant preferential modulation of EM or HF pigmentation. Matched cultures of EM and HFM were incubated with 2 bicyclic monoterpene diols, an aromatic glycerol ether, and a tyrosine kinase inhibitor (TKI). In addition, intact anagen VI HFs were incubated with these compounds in organ culture. Read-out parameters included melanogenesis, dendricity, proliferation and maintenance of anagen stage morphology. Results of this study showed that the TKI was more potent than the other test compounds in modulating melanocyte biology. Moreover, the TKI induced a greater increase in dendricity and melanogenesis in HFM compared to EM. The TKI induced the expression of tyrosinase protein in HFM, but not in EM. By contrast, the TKI markedly upregulated tyrosinase-related protein 2 (TRP-2) expression in EM, but not in HFM. Incubation of HF with diols in organ culture resulted in enhanced melanocyte status and anagen maintenance. In summary, we have identified compounds that can preferentially modulate the phenotype of melanocytes isolated from the HF. Thus, this model system should facilitate discovery of agents to specifically target skin or hair follicle pigmentation.