Keratinocytes synthesize and activate cortisol
Abstract
The bioavailability of circulating and/or endogenous hydrocortisone (cortisol) in epidermal cells is a key determinant in inflammatory disease and chronic wounds. It is not known, however, whether epidermal cells can regulate tissue cortisol and whether they are capable of producing endogenous glucocorticoids. In the present study, we show by microarray analysis that epidermal cells express mRNAs to all the major enzymes involved in the metabolic chain from cholesterol to cortisol, including cytocrome P450 chain, 11β-hydroxysteroid dehydrogenases (HSD11Bs), adrenocorticotropic hormone (ACTH) receptor (MC2R), and glucocorticoid receptor. The two enzymes mediating activation/deactivation of cortisone to cortisol, namely HSD11B1 and HSD11B2, were expressed at the protein level in cultured keratinocytes as well as human skin samples, as shown by Western blotting and immunohistochemistry, respectively. In functional assays, we show that keratinocytes are not only able to activate cortisone to cortisol in a HSD11B-dependent manner but also silencing of either HSD11B1 or HSD11B2 specifically modulates the bioavailability of the inactive glucocorticoid and the active steroid, respectively. A further key observation was that keratinocytes responded to stimulation with ACTH by a significant increase in the de novo synthesis of cortisol. Taken together, we provide evidence for a novel non-adrenal steroideal system in human keratinocytes.
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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 [64]
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 [64]
The equilibrium between 11βHSD1 and 11βHSD2 expression in skin together with sympathetic nerve density can maintain immunological homeostasis.
“The equilibrium between 11βHSD1 and 11βHSD2 expression in the skin together with sympathetic nerves density can maintain immunological homeostasis [1, 64, 150].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [64]
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- Authors
- Cirillo, N., & Prime, S. S.
- Affiliations
- University of Bristol (GB)
- Corresponding author
- Cirillo, Nicola
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2011-04-18
- Volume
- 112
- Issue
- 6
- Pages
- 1499-1505
- ISSN
- 0730-2312 (ISSN-L)
- 1097-4644
- OpenAlex
- W2020384245
- Cited by
- 118
- References
- 34
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 11 · 2016: 13 · 2015: 8 · 2014: 9 · 2013: 12 · 2012: 10
- FWCI
- 8.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Explore Bristol Research (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- keratinocytes, cortisol, cortisone, 11β-hydroxysteroid dehydrogenase, 11β-hydroxysteroid dehydrogenase type 1, 11β-hydroxysteroid dehydrogenase type 2, epidermis, steroidogenesis, ACTH, melanocortin 2 receptor, glucocorticoid receptor, cytochrome P450, chronic wounds, inflammation
- MeSH terms
- Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Humans, Hydrocortisone, Immunohistochemistry, Blotting, Western, Keratinocytes, Oligonucleotide Array Sequence Analysis, RNA, Small Interfering, 11-beta-Hydroxysteroid Dehydrogenases
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