Cutaneous Expression of CRH and CRH‐R: Is There a “Skin Stress Response System?”

AT Slominski, V Botchkarev… - Annals of the New …, 1999 - Wiley Online Library
AT Slominski, V Botchkarev, M Choudhry, N Fazal, K Fechner, J Furkert, E Krause, B Roloff…
Annals of the New York Academy of Sciences, 1999Wiley Online Library
The classical neuroendocrine pathway for response to systemic stress is by hypothalamic
release of corticotropin releasing hormone (CRH), subsequent activation of pituitary CRH
receptors (CRH‐R), and production and release of proopiomelanocortin (POMC) derived
peptides. It has been proposed that an equivalent to the hypothalamic‐pituitary‐adrenal axis
functions in mammalian skin, in response to local stress (see Reference 1). To further define
such system we used immunocytochemistry, RP‐HPLC separation, and RIA techniques, in …
Abstract
The classical neuroendocrine pathway for response to systemic stress is by hypothalamic release of corticotropin releasing hormone (CRH), subsequent activation of pituitary CRH receptors (CRH‐R), and production and release of proopiomelanocortin (POMC) derived peptides. It has been proposed that an equivalent to the hypothalamic‐pituitary‐adrenal axis functions in mammalian skin, in response to local stress (see Reference 1). To further define such system we used immunocytochemistry, RP‐HPLC separation, and RIA techniques, in rodent and human skin, and in cultured normal and malignant melanocytes and keratinocytes. Production of mRNA for CRH‐R1 was documented in mouse and human skin using RT‐PCR and Northern blot techniques; CRH binding sites and CRH‐R1 protein were also identified. Addition of CRH to immortalized human keratinocytes, and to rodent and human melanoma cells induced rapid, specific, and dose‐dependent increases in intracellular Ca2+. The latter were inhibited by the CRH antagonist α‐helical‐CRH(9–41) and by the depletion of extracellular calcium with EGTA. CRH production was enhanced by ultraviolet light radiation and forskolin (a stimulator for intracellular cAMP production), and inhibited by dexamethasone. Thus, evidence that skin cells, both produce CRH and express functional CRH‐R1, supports the existence of a local CRH/CRH‐R neuroendocrine pathway that may be activated within the context of a skin stress response system.
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