P20 ADRENOMEDULLIN: EPRESSION AND ROLE IN HUMAN SKIN AND HAIR FOLLICLE DIFFERENTIATION

¹Müller F.B., ²Müller-Röver S., ¹Korge B.P., ²Kapas S., ²Philpott M.P. ¹Dept. of Dermatology, Univ. of Cologne, Germany; ²Clinical Sciences Research Centre, Queen Mary and Westfield College, Univ. of London, Great Britain

Adrenomedullin (AM) is a regulatory peptide which is synthesized and secreted by a wide number of cells and tissues. AM is a potent vasodilator, but also exerts other functions, such as regulating cell growth and antimicrobial defence. Two receptors, L1 and CRLR, that are able to bind adrenomedullin, have been cloned and characterised.

Using immunohistochemistry, we have determined the distribution of AM and its receptors in human skin and during different stages of the hair cycle. AM immunoreactivity in inflammatory acne lesions was sued to evaluate the antimicrobial function of the protein and hair follicle cultures were performed to examine the role of AM in differentiation and proliferation of hair follicle keratinocytes. Strong immunoreactivity (IR) for AM and its receptors is present in the suprabasal epidermis, in the melanocytes of the epidermis and hairbulb, and in sweat and sebaceous glands. In the hair follicle, AM-protein is strongly expressed in the basal and suprabasal layers of the proximal outer root sheath. In the distal outer root sheath (ORS) expression is increasingly suprabasal especially in proximity to the bulge region where the basal cell layer is free of staining. While the CRLR receptor reveals a similar expression pattern, staining for L1 shows a suprabasal pattern of IR throughout the ORS. Similar expression of AM and its receptors was observed in catagen and early anagen follicles. In acne lesions AM expression is not markedly upregulated suggesting a minor role for this antimicrobial peptide in acne. Despite of its well documented mitogenic effects, particularly in oral and skin keratinocytes, AM had no significant effect of hair follicle growth in vitro. Further studies under modified culture conditions will address the role of AM on hair follicle differentiation.