9405242 Slominski Proopiomelanocortin (POMC) is the precursor of the biologically active neuropeptides adrenocorticotropin (ACTH), endorphins, melanotropins (MSH) and lipotropins (LPH). Although the gene coding for POMC is transcribed predominantly in the pituitary gland, its expression has also been detected in the central nervous system and in a variety of peripheral tissues including skin. The PI, therefore, hypothesizes that local (cutaneous) production of POMC peptides is a part of a system involved in the regulation of physiological responses of the skin. The main objective of the current research is to identify cutaneous cells expressing proopiomelanocortin (POMC), to correlate POMC expression and processing with the cyclic activity of hair follicles, to test whether corticotropin releasing hormone (CRH) and glucocorticoids regulate production of POMC peptides and to detect and characterize CRH receptors. To realize this goal, molecular, biochemical, immunocytochenical and cell biology techniques will be utilized. The realization of the project will support the concept that peripheral POMC activity may be an integral part of the biological clock regulating cyclic activity of hair follicles and periodic changes of skin physiology. It is already accepted that residential cells of the skin respond phenotypically to ACTH and MSH, that there is a skin associated immune system and the beta-endorphin, MSH and ACTH can act as immunomodulators. Therefore, it appears that local production of POMC peptides may be a part of signals regulating physiological responses of the skin. ***