P#56  Pro-opiomelanocortin peptides and the regulation of the human hair follicle pigmentary unit

S. Kauser1, K.U. Schallreuter1, A.J. Thody1, C. Gummer2 and D.J. Tobin1
1Dept of Biomedical Sciences, University of Bradford, West Yorkshire and 2Procter & Gamble Ltd., Surrey, England

Pro-opiomelanocortin (POMC) is cleaved by pro-hormone convertases (PC)
1 and 2 to yield ACTH and a-MSH respectively. These peptides are produced locally in the skin and participate in several important cutaneous functions including immunomodulation, neurotransmission and melanogenesis. POMC melanogenic effects are mediated via the MC-1 receptor (MC-1R). While the involvement of these POMC peptides in the regulation of murine hair pigmentation has been well documented, little is known about the role of a-MSH and ACTH in human hair pigmentation. This study was designed to assess immunohisto(cyto)chemically the expression of a-MSH, ACTH as well as PC1 and PC2 in frozen sections of normal haired scalp and in cultures of normal human scalp hair follicle melanocytes (HFM). The expression of POMC, PC1 & PC2 genes and MC-1R gene was analysed by RT-PCR in HFM cultures. Additionally, a functional role for these peptides was investigated by stimulation of HFM cultures with a-MSH and ACTH for 72 hours. ACTH was expressed by a minor sub-population of gp100-positive melanogenic melanocytes located in the anagen hair bulb. By contrast, a-MSH was not expressed by any gp100-positive HFM. Expression of the POMC processing enzymes, PC1 and PC2, was confined to gp-100 positive melanocytes located in the most proximal and peripheral matrix of the anagen hair bulb. Variable expression of a-MSH, ACTH and PC1 & PC2 was observed in primary HFM cultures, with the strongest expression detected in proliferating/differentiating melanocytes containing little melanin. POMC, PC1, PC2 and MC-1R mRNA was detected in HFM cultures. Both a-MSH and ACTH significantly increased melanogenesis, proliferation and dendricity in functional studies. This study shows that both a-MSH and ACTH exhibit potent melanogenic, mitogenic and dendritogenic effects in cultured HFM. Their differential expression in the anagen hair follicle in situ suggests that these peptides may play a role in the regulation of HFM differentiation during anagen and also during hair cycling.