Characterization of a ultraviolet B-induced corticotropin-releasing hormone-proopiomelanocortin system in human melanocytes
Open accessAbstract
CRH, the main regulator of the systemic response to stress, is also expressed in the skin where it is incorporated into a local homolog of the hypothalamic-pituitary-adrenal axis. To investigate the mechanisms of the induction of the CRH-proopiomelanocortin (POMC) response in human melanocytes, we used UVB as an epidermal-specific stressor. Human normal melanocytes cultured in vitro were irradiated with graded doses of UVB, and the CRH-POMC responses were measured in cell extracts and/or supernatants. UVB stimulated the CRH promoter, the CRH mRNA expression, and peptide release. The UVB-induced stimulation of the CRH promoter was suppressed by pharmacological inhibitors of protein kinase A or by plasmid overexpressing a dominant mutant cAMP response element (CRE)-binding protein (CREB). UVB also stimulated phosphorylation of CREB, binding of phosphorylated CREB to CRE sites in the CRH promoter, and activity of the reporter gene construct driven by consensus CRE sites. Mutation in the CRE site in the CRH promoter rendered the corresponding reporter gene construct less responsive to UVB in both normal and malignant melanocytes. In addition to CRH effects, UVB activated the POMC promoter, POMC mRNA expression, and ACTH release, whereas an antagonist of the CRH receptor 1 abrogated the UVB-stimulated induction of POMC. In conclusion, UVB induces CRH production in human melanocytes through stimulation of the protein kinase A pathway, with sequential involvement of CRH-CRH receptor 1 in the stimulation of POMC expression.
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UVB/UVC stimulation of CYP11A1 is accompanied by upregulation of CRF, urocortin, and POMC-derived peptides.
“This stimulation was accompanied by upregulation of the production of corticotropin releasing factor (CRF), urocortin (Unc) and POMC derived peptides”
From The role of CYP11A1 in the production of vitamin D metabolites and their role in the regulation of epidermal functions (2014) · cites this paper as [33]
Pharmacological inactivation of CRH-R1 by selective inhibitors abrogated UVB-stimulated induction of POMC production.
“Pharmacological inactivation of CRH-R1 by selective inhibitors abrogated the UVB-stimulated induction of POMC production [156].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [156]
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- Authors
- Zbytek, B., Wortsman, J., & Slominski, A.
- Affiliations
- University of Tennessee Health Science Center (US)
- SIU Medicine (US)
- Corresponding author
- Slominski, Andrzej
- ORCID
- Slominski, Andrzej
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2006-10-01
- Volume
- 20
- Issue
- 10
- Pages
- 2539-2547
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- PMC
- PMC1847418
- OpenAlex
- W2022074542
- Cited by
- 60
- References
- 44
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2022: 2 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 6 · 2012: 5
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-052190, AR 047079, R01AR052190, R01AR047079)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- UV-B radiation, corticotropin-releasing factor, proopiomelanocortin, human melanocytes, hypothalamic-pituitary-adrenal axis, protein kinase A, CREB phosphorylation, cAMP response element, CRH receptor 1, ACTH release, melanoma
- MeSH terms
- Corticotropin-Releasing Hormone, Flow Cytometry, Gene Expression Regulation, Humans, Melanocytes, Mutation, Phosphorylation, Pro-Opiomelanocortin, Promoter Regions, Genetic, Ultraviolet Rays, Blotting, Western, Signal Transduction, Cyclic AMP-Dependent Protein Kinases, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Electrophoretic Mobility Shift Assay, CREB-Binding Protein
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