Cutaneous Expression of CRH and CRH‐R: Is There a “Skin Stress Response System?”
Abstract
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 Ca 2+. 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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UVB has a similar stimulatory effect on CRH and POMC signaling, production of cortisol, and inhibition of the GR.
“UVB (280–320 nm), a recognized stimulator of melanin pigmentation [152], has similar stimulatory effect on CRH and POMC signaling, production of cortisol and inhibition of the GR [81, 129, 131, 151, 153, 154].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [153]
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Cites
Ultraviolet B stimulates production of corticotropin releasing factor (CRF) by human melanocytes
Slominski, A., Baker, J., Ermak, G., Chakraborty, A., & Pawelek, J. (1996) · FEBS Letters · doi:10.1016/s0014-5793(96)01315-4 · Cited by 78 · see citing works
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Slominski, A., Wortsman, J., Luger, T., Paus, R., & Solomon, S. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.3.979 · Cited by 776 · see citing works
Self-citationIto, N., Ito, T., Kromminga, A., Bettermann, A., Takigawa, M., Kees, F., Straub, R. H., & Paus, R. (2005) · The FASEB Journal · doi:10.1096/fj.04-1968fje · Cited by 498 · see citing works
Self-citationSlominski (2012) · doi:10.1007/978-3-642-19683-6_1 · Cited by 461 · see citing works
Key role of CRF in the skin stress response system
Slominski, A. T., Zmijewski, M. A., Zbytek, B., Tobin, D. J., Theoharides, T. C., & Rivier, J. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1092 · Cited by 400 · see citing works
Self-citationSteroidogenesis in the skin: Implications for local immune functions
Slominski, A., Zbytek, B., Nikolakis, G., Manna, P. R., Skobowiat, C., Zmijewski, M., Li, W., Janjetovic, Z., Postlethwaite, A., Zouboulis, C. C., et al. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.02.006 · Cited by 369 · see citing works
Self-citationCutaneous expression of corticotropin-releasing hormone (CRH), urocortin, and CRH receptors
SLOMINSKI, A., WORTSMAN, J., PISARCHIK, A., ZBYTEK, B., LINTON, E. A., MAZURKIEWICZ, J. E., & WEI, E. T. (2001) · The FASEB Journal · doi:10.1096/fj.00-0850rev · Cited by 305 · see citing works
Self-citationDifferential expression of HPA axis homolog in the skin
Slominski, A., Wortsman, J., Tuckey, R. C., & Paus, R. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.12.012 · Cited by 279 · see citing works
Self-citationCorticotropin releasing hormone and the skin
Slominski, A. (2006) · Frontiers in bioscience · doi:10.2741/1966 · Cited by 157 · see citing works
Self-citationUVB activates hypothalamic-pituitary-adrenal axis in C57BL/6 mice
Skobowiat, C., & Slominski, A. T. (2015) · Journal of Investigative Dermatology · doi:10.1038/jid.2014.450 · Cited by 126 · see citing works
Self-citationHiroi, N., Wong, M. L., Licinio, J., Park, C., Young, M., Gold, P. W., Chrousos, G. P., & Bornstein, S. R. (2001) · Molecular Psychiatry · doi:10.1038/sj.mp.4000908 · Cited by 124 · see citing works
Skin as an endocrine organ: implications for its function
Slominski, A., Wortsman, J., Paus, R., Elias, P. M., Tobin, D. J., & Feingold, K. R. (2008) · Drug Discovery Today Disease Mechanisms · doi:10.1016/j.ddmec.2008.04.004 · Cited by 116 · see citing works
Self-citationStress-linked cortisol concentrations in hair: what we know and what we need to know
Sharpley, C. F., McFarlane, J. R., & Slominski, A. (2012) · revneuro · doi:10.1515/rns.2011.058 · Cited by 92 · see citing works
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- Authors
- SLOMINSKI, A. T., BOTCHKAREV, V., CHOUDHRY, M., FAZAL, N., FECHNER, K., FURKERT, J., KRAUSE, E., ROLOFF, B., SAYEED, M., WEI, E., ZBYTEK, B., ZIPPER, J., WORTSMAN, J., & PAUS, R.
- Affiliations
- Loyola University Medical Center (US)
- Humboldt-Universität zu Berlin (DE)
- University of California, Berkeley (US)
- Gdańsk Medical University (PL)
- SIU Medicine (US)
- Corresponding author
- SLOMINSKI, ANDRZEJ T.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 1999-10
- Volume
- 885
- Issue
- 1
- Pages
- 287-311
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W2014198790
- Cited by
- 147
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 8 · 2013: 5 · 2012: 7
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- corticotropin-releasing factor, CRH receptor 1, hypothalamic-pituitary-adrenal axis, melanocytes, keratinocytes, melanoma, intracellular calcium, ultraviolet radiation, forskolin, dexamethasone
- MeSH terms
- Animals, Cells, Cultured, Corticotropin-Releasing Hormone, Humans, Melanocytes, Models, Biological, Pro-Opiomelanocortin, Skin Neoplasms, Skin Physiological Phenomena, Transcription, Genetic, Keratinocytes, Receptors, Corticotropin-Releasing Hormone, Mice
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