Localization, Age- and Site-Dependent Expression, and Regulation of 11β-Hydroxysteroid Dehydrogenase Type 1 in Skin
Open accessAbstract
Glucocorticoids (GCs) are highly detrimental to skin integrity and function both when applied topically for anti-inflammatory treatments and during conditions of circulating excess, e.g., Cushing's syndrome. Within target tissues, GC availability is regulated at a prereceptor level, independently of systemic levels, by isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) that interconvert active cortisol and inactive cortisone. Many of the adverse effects of GCs on skin are also reminiscent of the natural aging process. 11β-HSD1 (which activates cortisol), but not 11β-HSD2 (which inactivates cortisol), was expressed in epidermal keratinocytes and dermal fibroblasts in human skin and also in outer hair follicle root sheath cells in murine skin. 11β-HSD1 activity was present ex vivo in both species and increased with age in human skin tissue explants. In primary human dermal fibroblasts (HDF) from both photoprotected and photoexposed sites, 11β-HSD1 also increased with donor age. Additionally, photoexposed HDF displayed higher 11β-HSD1 mRNA expression than donor-matched photoprotected HDF. GC treatment of HDF caused upregulation of 11β-HSD1 mRNA levels independent of donor age or site. The age- and site-associated increase in dermal 11β-HSD1, and the ensuing increased local GC activation, may contribute to the adverse changes in skin morphology and function associated with chronological aging and photoaging.
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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 [66]
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 [66]
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- Authors
- Tiganescu, A., Walker, E. A., Hardy, R. S., Mayes, A. E., & Stewart, P. M.
- Affiliations
- University of Birmingham (GB)
- Unilever (United Kingdom) (GB)
- Corresponding author
- Stewart, Paul M.
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 131
- Issue
- 1
- Pages
- 30-36
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2003953254
- Cited by
- 122
- References
- 48
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 10 · 2022: 5 · 2021: 6 · 2020: 9 · 2019: 4 · 2018: 10 · 2017: 11 · 2016: 12 · 2015: 11 · 2014: 10 · 2013: 13 · 2012: 10
- FWCI
- 10.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- European Research Council
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Keywords
- 11β-hydroxysteroid dehydrogenase type 1, glucocorticoid metabolism, skin aging, photoaging, dermal fibroblasts, keratinocytes, cortisol, Cushing's syndrome, topical corticosteroids, gene expression regulation
- MeSH terms
- Animals, Carbohydrate Dehydrogenases, Cells, Cultured, Epidermis, Fibroblasts, Glucocorticoids, Humans, Immunohistochemistry, Organ Culture Techniques, Receptors, Glucocorticoid, Skin Aging, Keratinocytes, Mice, Knockout, Dermis, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Mice
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