9604364 Slominski The most important response to stress is the activation of the hypothalamic-pituitary-adrenal (HPA)axis, which is composed of the corticotropin releasing hormone (CRH), the proopiomelanocortin (POMC) derived peptides including ACTH and MSH and of a feedback inhibitory mechanism executed by glucocorticoids. Recent data provide evidence that above factors are produced by skin. Therefore, the PI will test the hypothesis that cutaneous homeostasis is regulated through a local immunoneuroendocrine loop involving activation of the CRH-POMC axis and its termination by glucocorticoids. The PI will also investigate a relation between local (skin) and systemic endocrine systems. To address those problems the PI will use the C57BL/6 mouse model in which the cyclic activity of the hair follicle affects the metabolic state of the skin. It has been already postulated that local production of POMC peptides may be a part of signals regulating physiological responses of the skin, for example hair growth, or represent deregulated circuits in pathologic conditions, for example inflammatory diseases and cancer. In this proposal, a complex neuroendocrine regulation will be studied in depth in a simple model such as the rodent hair cycle so that the larger questions of environmental regulation of biological rhythms and neuroendocrine and neuroimmunological functions by POMC peptides and CRH receptors in the skin can be elucidated. ***
