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Title: EXPRESSION OF ADRENOMEDULLIN AND ITS RECEPTOR IN NORMAL AND MALIGNANT SKIN AND THEIR POTENTIAL PLURIPOTENT ROLE.

Author
item MARTINEZ, A. - NIH, NCI, ROCKVILLE, MD
item Elsasser, Theodore
item MURO-CACHO, C. - U. SOUTH. FL, CANCER CTR.
item MOODY, T. - NIH, NCI, ROCKVILLE, MD
item MILLER, M. - NIH, NCI, ROCKVILLE, MD
item MACRI, C. - U.S.U.H.S., BETHESDA, MD
item CUTTITTA, F. - NIH, NCI, ROCKVILLE, MD

Submitted to: Journal of Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: The skin is the first line of defense against invading microbes. For a significant period of time questions were raised as to how the skin could be so effective in preventing infection when so blatantly challenged with different germs. It was recognized that reptiles and other nonmammalian species had antimicrobial substances in their skin, some of which existed as small peptides. In addition, it was known that tissues in the oral cavity had bacteriocidal and bacteriostatic properties. In an initial survey of tissues we discovered that the peptide adrenomedullin was present in the skin. Investigators had earlier determined that AM in the tissues of the mouth, have antimicrobial activity. In this paper we determined that AM is present throughout the skin of humans and is also secreted into the sweat in concentrations significantly greater than those measured in blood. The study shows that adrenomedullin may have a function in maintaining health through its ability to kill bacteria in the skin and promote skin growth and repair.

Technical Abstract: Adrenomedullin (AM) is a multifunctional peptide involved in a variety of physiological functions including growth regulation and antimicrobial activity. We have determined by immunohistochemistry and in situ hybridization that AM and its receptor are present in all the epithelial cells of the normal skin, including keratinocytes or the epidermis and hair follicles, as well as cells of the glands and secretory ducts. We have also detected AM in the sweat by radioimmunoassay. In addition, AM and its receptor were found in skin tumors with different histologies. The presence of AM and its receptor in normal and neoplastic skin was confirmed by RT-PCR and Western blot analysis performed on cell extracts from human skin cell lines. Radiolabelled AM bound to specific sites in cultured cells and its binding was blocked by the addition of nonlabelled AM but not by related peptides such as A<(22-52), PAMP, CGRP, CGRP(8-37), or amylin. Finally, exposure to synthetic AM resulted in an increase of thymidine uptake by skin cells. These results are consistent with the role of AM as an antimicrobial peptide and offers promise as an effector of wound healing.