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Cited by 79Dermatology and Skin DiseasesAdrenal Hormones and DisordersCholesterol and Lipid Metabolism

Cutaneous glucocorticosteroidogenesis: securing local homeostasis and the skin integrity

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Slominski, Andrzej T., Manna, Pulak R., Tuckey, Robert C.·2014·Experimental Dermatology
DOI 10.1111/exd.12376PMC PMC4046116
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Abstract

Human skin has the ability to synthesize glucocorticoids de novo from cholesterol or from steroid intermediates of systemic origin. By interacting with glucocorticoid receptors, they regulate skin immune functions as well as functions and phenotype of the epidermal, dermal and adnexal compartments. Most of the biochemical (enzyme and transporter activities) and regulatory (neuropeptides mediated activation of cAMP and protein kinase A dependent pathways) principles of steroidogenesis in the skin are similar to those operating in classical steroidogenic organs. However, there are also significant differences determined by the close proximity of synthesis and action (even within the same cells) allowing para-, auto- or intracrine modes of regulation. We also propose that ultraviolet light B (UVB) can regulate the availability of 7-dehydrocholesterol for transformation to cholesterol with its further metabolism to steroids, oxysterols or ∆7 steroids, because of its transformation to vitamin D3. In addition, UVB can rearrange locally produced ∆7 steroids to the corresponding secosteroids with a short- or no-side chain. Thus, different mechanisms of regulation occur in the skin that can be either stochastic or structuralized. We propose that local glucocorticosteroidogenic systems and their regulators, in concert with cognate receptors operate to stabilize skin homeostasis and prevent or attenuate skin pathology.

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  • Organs expressing lower levels of CYP11A1 such as skin and gastrointestinal tract can metabolize vitamin D3 through the novel CYP11A1-initiated pathway, as an additional and alternative pathway to the classical one.

    “These data indicate that organs expressing lower levels of CYP11A1 such as skin [15,66] and gastrointestinal (GI) tract [111] can metabolize D3 through the novel CYP11A1-initiated pathway, as an additional and alternative pathway to the classical one.”

    From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [66]

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Authors
Slominski, A. T., Manna, P. R., & Tuckey, R. C.
Affiliations
  • University of Tennessee Health Science Center (US)
  • Texas Tech University (US)
  • The University of Western Australia (AU)
Corresponding author
Slominski, Andrzej T.
ORCID
Venue
Experimental Dermatology
Publisher
Wiley
Published
2014-05-28
Volume
23
Issue
6
Pages
369-374
ISSN
  • 0906-6705 (ISSN-L)
  • 1600-0625
DOI
10.1111/exd.12376
PMC
PMC4046116
OpenAlex
W2052241333
Cited by
79
References
131
Citations by year
2026: 3 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 10 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 11 · 2014: 6
FWCI
12.43
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Experimental Dermatology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • UWA Profiles and Research Repository (UWA) (submittedVersion)
Funders
  • National Science Foundation (0918934)
  • National Institutes of Health
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (2R01AR052190-A6, R01AR052190, R01AR056666)
Topics
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
glucocorticoid receptor, 7-dehydrocholesterol, UV-B radiation, vitamin D3, oxysterols, secosteroids, skin homeostasis, skin immune function, epidermis, cAMP/PKA signaling
MeSH terms
Adrenal Cortex Hormones, Glucocorticoids, Homeostasis, Humans, Skin, Skin Physiological Phenomena, Ultraviolet Rays

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