EXPRESSION OF ADRENOMEDULLIN AND ITS RECEPTOR IN NORMAL AND MALIGNANTHUMAN SKIN - A POTENTIAL PLURIPOTENT ROLE IN THE INTEGUMENT

Adrenomedullin (AM) is a multifunctional peptide involved in a variety of physiological functions, including growth regulation and antimicro bial activity. We have determined by immunohistochemistry and in situ. hybridization that AM and its receptor are present in all the epithel ial cells of the normal skin, including keratinocytes of the epidermis and hair follicles, as well as cells of the glands and secretory duct s. We also have detected AM in the sweat, by RIA. In addition, AM and its receptor were found in skin tumors of different histologies. The p resence of AM and its receptor in normal and neoplastic skin was confi rmed by RT-PCR and Western blot analysis performed on cell extracts fr om human skin cell lines. Radiolabeled AM bound to specific sites in c ultured cells with a K-d of 9 nM. This binding was blocked by the addi tion of cold AM but not by related peptides such as AM 22-52, pro-AM 2 0 N-terminal peptide, calcitonin gene-related peptide, calcitonin gene -related peptide 8-37, or amylin. Finally, exposure to synthetic AM re sulted in an increase of thymidine intake by skin cells. These results implicate AM as a potential player in skin defense against infectious microorganisms and as a possible autocrine growth factor in normal sk in physiology and tumor development.