Steroid synthesis by primary human keratinocytes; implications for skin disease
Abstract
Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3βHSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7-(3)H]-pregnenolone through each steroid intermediate to [7-(3)H]-cortisol in cultured PHK. Trilostane (a 3βHSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data show that PHK are capable of extra-adrenal cortisol synthesis, which could be a fundamental pathway in skin biology with implications in psoriasis and atopic dermatitis.
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Epidermal keratinocytes express the cholesterol transporters TSPO and MLN64.
“In addition to StAR, epidermal keratinocytes also express cholesterol transporters TSPO and MLN64 [54, 63].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [63]
StAR expression has been detected in epidermal keratinocytes, sebocytes, outer root sheath of hair follicles, vascular tissues, and eccrine ducts.
“The expression of StAR has been detected by RT-PCR and immunohistochemical analyses in epidermal keratinocytes, sebocytes, outer root sheath of hair follicles (HFs), vascular tissues and eccrine ducts [62, 63, 69, 84].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [63]
StAR expression is decreased or absent in psoriatic and atopic dermatitis skin compared with normal skin.
“StAR expression has been demonstrated to be decreased or absent in psoriatic and atopic dermatitis when compared to normal skin tissues [62, 63].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [63]
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- Authors
- Hannen, R. F., Michael, A. E., Jaulim, A., Bhogal, R., Burrin, J. M., & Philpott, M. P.
- Affiliations
- Queen Mary University of London (GB)
- University of London (GB)
- Unilever (United Kingdom) (GB)
- Corresponding author
- Hannen, Rosalind F.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 404
- Issue
- 1
- Pages
- 62-67
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W1969061052
- Cited by
- 96
- References
- 21
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 11 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 4 · 2015: 11 · 2014: 5 · 2013: 9 · 2012: 9
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- keratinocytes, cortisol production, pregnenolone metabolism, CYP11A1, CYP17A1, CYP21, CYP11B1, steroidogenic acute regulatory protein, MLN64, cholesterol transport, psoriasis, atopic dermatitis, trilostane, ketoconazole
- MeSH terms
- Cells, Cultured, Dermatitis, Atopic, Epidermis, Humans, Hydrocortisone, Pregnenolone, Psoriasis, Steroid Hydroxylases, 3-Hydroxysteroid Dehydrogenases, Keratinocytes
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