Cutaneous expression of CRH and CRH-R. Is there a 'skin stress response system?'

Andrzej T. Slominski, Vladimir Botchkarev, Mashkoor Choudhry, Nadeem Fazal, Klaus Fechner, Jens Furkert, Eberhart Krause, Birgit Roloff, Mohammad Sayeed, Edward Wei, Blazej Zbytek, Josef Zipper, Jacobo Wortsman, Ralf Paus

Research output: Contribution to journalArticlepeer-review

116 Scopus citations


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 contest of a skin stress response system.

Original languageEnglish (US)
Pages (from-to)287-311
Number of pages25
JournalAnnals of the New York Academy of Sciences
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science


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