Ultraviolet radiation regulates cortisol activity in a waveband-dependent manner in human skin ex vivo: Ultraviolet radiation regulates cutaneous cortisol activity
Open accessAbstract
BACKGROUND: 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), and glucocorticoids (GC) and their receptor (GR) play a key role in tissue-specific regulation of GC action. OBJECTIVES: To determine the expression of genes encoding 11β-HSD1 (HSD11B1), 11β-HSD2 (HSD11B2) and GR (GRα; also known as NC3R1) and their protein products, and levels of cortisol in human skin explants and/or cocultured keratinocytes/melanocytes after treatment with ultraviolet (UV) A, B or C wavebands. METHODS: Skin from foreskins and/or cocultured human keratinocytes/melanocytes were irradiated with UVA, UVB or UVC (skin) and incubated for 12 and 24 h. Methods of reverse transcription-polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay and immunohistochemistry (IHC) were used to determine expression and localization of corresponding genes or antigens. RESULTS: UVB enhanced the HSD11B1 gene and protein expression in a dose-dependent manner, while UVA had no effect. Similarly, UVC increased 11β-HSD1 protein product as measured by IHC. UVB and UVC enhanced cortisol production and decreased epidermal GR expression, while UVA had no detectable effects. Although both UVA and UVB stimulated HSD11B2 gene expression, only UVA increased 11β-HSD2 protein product levels with UVB and UVC having no effect. CONCLUSIONS: We suggest that these differential, waveband-dependent effects of UV radiation on the expression of cutaneous HSD11B1, HSD11B2 and GRα genes and their corresponding protein products, and cortisol production are to protect and/or restore the epidermal barrier homeostasis against disruption caused by the elevated cortisol level induced by UVB and UVC.
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Skin expresses 11βHSD2, which oxidizes cortisol to inactive cortisone.
“Skin also expresses 11βHSD2 which works in the oxidative direction, converting cortisol to the inactive cortisone [23, 64–66, 81].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [81]
Intracellular conversion by 11βHSD1 and 11βHSD2 together with GR activity is a key mechanism of tissue-specific regulation of glucocorticoid action contributing to glucocorticoid deficiency.
“Recent studies have demonstrated that intracellular conversion, performed by these two enzymes, together with GR activity, represent a key mechanism of tissue-specific regulation of GC action contributing to GC deficiency, which constitutes a big challenge in dermatology [64, 66, 81, 148, 149].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [81]
UVA had no effect on cortisol, CRH, and ACTH production but stimulated β-endorphin and 11βHSD2 expression.
“UVA (320–400 nm) had no effect on cortisol, CRH and ACTH production but stimulated β-endorphin and 11βHSD2 expression [81, 151, 155].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [81]
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 [81]
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Self-citation
- Authors
- Skobowiat, C., Sayre, R. M., Dowdy, J. C., & Slominski, A. T.
- Affiliations
- University of Tennessee Health Science Center (US)
- Corresponding author
- Slominski, A.T.
- Venue
- British Journal of Dermatology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-01-31
- Volume
- 168
- Issue
- 3
- Pages
- 595-601
- ISSN
- 0007-0963 (ISSN-L)
- PMC
- PMC3586986
- OpenAlex
- W1899539978
- Cited by
- 115
- References
- 28
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 8 · 2023: 11 · 2022: 6 · 2021: 6 · 2020: 10 · 2019: 5 · 2018: 7 · 2017: 12 · 2016: 19 · 2015: 7 · 2014: 9 · 2013: 6
- FWCI
- 16.04
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- British Journal of Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR052190, R01AR056666)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- ultraviolet radiation, cortisol, 11β-hydroxysteroid dehydrogenase type 1, 11β-hydroxysteroid dehydrogenase type 2, glucocorticoid receptor, UV-B radiation, UVA, UV-C, skin explants, keratinocytes, melanocytes, skin barrier, gene expression, human skin
- MeSH terms
- Cells, Cultured, Glucocorticoids, Homeostasis, Humans, Hydrocortisone, Melanocytes, Radiation Dosage, Receptors, Glucocorticoid, Skin, Ultraviolet Rays, Keratinocytes, 11-beta-Hydroxysteroid Dehydrogenase Type 1, 11-beta-Hydroxysteroid Dehydrogenase Type 2
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