Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin

doi:10.1016/j.jid.2024.04.022

Review

. 2024 Oct;144(10):2145-2161.

doi: 10.1016/j.jid.2024.04.022. Epub 2024 Jul 12.

Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin

Andrzej T Slominski¹, Tae-Kang Kim², Zorica Janjetovic², Radomir M Slominski³, Wei Li⁴, Anton M Jetten⁵, Arup K Indra⁶, Rebecca S Mason⁷, Robert C Tuckey⁸

Affiliations

¹ Department of Dermatology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA; Cancer Chemoprevention Program, Comprehensive Cancer Center, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA; Veterans Administration Medical Center, Birmingham, Alabama, USA. Electronic address: aslominski@uabmc.edu.
² Department of Dermatology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
³ Department of Genetics, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁴ Drug Discovery Center, Department of Pharmaceutical Sciences, University of Tennessee Health Science Center College of Pharmacy, Memphis, Tennessee, USA.
⁵ Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
⁶ Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA; Department of Dermatology, Oregon Health and Science University, Portland, Oregon, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon; USA.
⁷ School of Life and Environmental Sciences, The University of Sydney, Australia; Charles Perkins Centre, The University of Sydney, Australia.
⁸ School of Molecular Sciences, The University of Western Australia, Perth, Australia.

PMID: 39001720
PMCID: PMC11416330 (available on 2025-10-01)
DOI: 10.1016/j.jid.2024.04.022

Review

Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin

Andrzej T Slominski et al. J Invest Dermatol. 2024 Oct.

. 2024 Oct;144(10):2145-2161.

doi: 10.1016/j.jid.2024.04.022. Epub 2024 Jul 12.

Authors

Andrzej T Slominski¹, Tae-Kang Kim², Zorica Janjetovic², Radomir M Slominski³, Wei Li⁴, Anton M Jetten⁵, Arup K Indra⁶, Rebecca S Mason⁷, Robert C Tuckey⁸

Affiliations

¹ Department of Dermatology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA; Cancer Chemoprevention Program, Comprehensive Cancer Center, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA; Veterans Administration Medical Center, Birmingham, Alabama, USA. Electronic address: aslominski@uabmc.edu.
² Department of Dermatology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
³ Department of Genetics, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁴ Drug Discovery Center, Department of Pharmaceutical Sciences, University of Tennessee Health Science Center College of Pharmacy, Memphis, Tennessee, USA.
⁵ Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
⁶ Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA; Department of Dermatology, Oregon Health and Science University, Portland, Oregon, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon; USA.
⁷ School of Life and Environmental Sciences, The University of Sydney, Australia; Charles Perkins Centre, The University of Sydney, Australia.
⁸ School of Molecular Sciences, The University of Western Australia, Perth, Australia.

PMID: 39001720
PMCID: PMC11416330 (available on 2025-10-01)
DOI: 10.1016/j.jid.2024.04.022

Abstract

Novel pathways of vitamin D3, lumisterol 3 (L3), and tachysterol 3 (T3) activation have been discovered, initiated by CYP11A1 and/or CYP27A1 in the case of L3 and T3. The resulting hydroxymetabolites enhance protection of skin against DNA damage and oxidative stress; stimulate keratinocyte differentiation; exert anti-inflammatory, antifibrogenic, and anticancer activities; and inhibit cell proliferation in a structure-dependent manner. They act on nuclear receptors, including vitamin D receptor, aryl hydrocarbon receptor, LXRα/β, RAR-related orphan receptor α/γ, and peroxisome proliferator-activated receptor-γ, with selectivity defined by their core structure and distribution of hydroxyl groups. They can activate NRF2 and p53 and inhibit NF-κB, IL-17, Shh, and Wnt/β-catenin signaling. Thus, they protect skin integrity and physiology.

Keywords: Lumisterol; Nuclear receptors; Skin; Tachysterol; Vitamin D receptors.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest.

Cited by

Melatonin and the Skin: Current Progress and Perspectives for Human Health.
Slominski AT, Kim TK, Janjetovic Z, Slominski RM, Ganguli-Indra G, Athar M, Indra AK, Reiter RJ, Kleszczyński K. Slominski AT, et al. J Invest Dermatol. 2025 Jun;145(6):1345-1360.e2. doi: 10.1016/j.jid.2024.11.012. Epub 2025 Feb 6. J Invest Dermatol. 2025. PMID: 39918482 Review.
Beneficial health effects of ultraviolet radiation: expert review and conference report.
Riedmann U, Dibben C, de Gruijl FR, Gorman S, Hart PH, Hoel DG, Levy C, Lindqvist PG, Norval M, Parikh SS, Pilz S, Rueter K, Slominski AT, Slominski RM, Young AR, Zgaga L, Weller RB. Riedmann U, et al. Photochem Photobiol Sci. 2025 Jun;24(6):867-893. doi: 10.1007/s43630-025-00743-6. Epub 2025 Jun 4. Photochem Photobiol Sci. 2025. PMID: 40465176 Review.
Antioxidant Functions of Vitamin D and CYP11A1-Derived Vitamin D, Tachysterol, and Lumisterol Metabolites: Mechanisms, Clinical Implications, and Future Directions.
Vázquez-Lorente H, Herrera-Quintana L, Jiménez-Sánchez L, Fernández-Perea B, Plaza-Diaz J. Vázquez-Lorente H, et al. Antioxidants (Basel). 2024 Aug 17;13(8):996. doi: 10.3390/antiox13080996. Antioxidants (Basel). 2024. PMID: 39199241 Free PMC article. Review.
Relation of T Cell Profile with Vitamin D Receptor and Vitamin D-Binding Protein Gene Polymorphisms in Atopy.
Bastyte D, Tamasauskiene L, Stakaitiene I, Briede K, Ugenskiene R, Valiukeviciene S, Gradauskiene B. Bastyte D, et al. Int J Mol Sci. 2024 Aug 20;25(16):9021. doi: 10.3390/ijms25169021. Int J Mol Sci. 2024. PMID: 39201708 Free PMC article.
Slit1 Promotes Hypertrophic Scar Formation Through the TGF-β Signaling Pathway.
Cui HS, Zheng YX, Cho YS, Ro YM, Jeon K, Joo SY, Seo CH. Cui HS, et al. Medicina (Kaunas). 2024 Dec 12;60(12):2051. doi: 10.3390/medicina60122051. Medicina (Kaunas). 2024. PMID: 39768930 Free PMC article.

See all "Cited by" articles

References

1. Azin M, Ngo KH, Hojanazarova J, Demehri S. Topical Calcipotriol Plus Imiquimod Immunotherapy for Nonkeratinocyte Skin Cancers. JID Innov 2023;3(6):100221. - PMC - PubMed
1. Becker AL, Carpenter EL, Slominski AT, Indra AK. The Role of the Vitamin D Receptor in the Pathogenesis, Prognosis, and Treatment of Cutaneous Melanoma. Front Oncol 2021;11:743667. - PMC - PubMed
1. Bikle D, Christakos S. New aspects of vitamin D metabolism and action - addressing the skin as source and target. Nat Rev Endocrinol 2020. - PubMed
1. Bikle DD. Vitamin D receptor, UVR, and skin cancer: a potential protective mechanism. J Invest Dermatol 2008;128(10):2357–61. - PMC - PubMed
1. Bikle DD. The vitamin D receptor: a tumor suppressor in skin. Adv Exp Med Biol 2014;810:282–302. - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
- Elsevier Science
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

[1] Azin M, Ngo KH, Hojanazarova J, Demehri S. Topical Calcipotriol Plus Imiquimod Immunotherapy for Nonkeratinocyte Skin Cancers. JID Innov 2023;3(6):100221. - PMC - PubMed

[2] Azin M, Ngo KH, Hojanazarova J, Demehri S. Topical Calcipotriol Plus Imiquimod Immunotherapy for Nonkeratinocyte Skin Cancers. JID Innov 2023;3(6):100221. - PMC - PubMed

[3] Becker AL, Carpenter EL, Slominski AT, Indra AK. The Role of the Vitamin D Receptor in the Pathogenesis, Prognosis, and Treatment of Cutaneous Melanoma. Front Oncol 2021;11:743667. - PMC - PubMed

[4] Becker AL, Carpenter EL, Slominski AT, Indra AK. The Role of the Vitamin D Receptor in the Pathogenesis, Prognosis, and Treatment of Cutaneous Melanoma. Front Oncol 2021;11:743667. - PMC - PubMed

[5] Bikle D, Christakos S. New aspects of vitamin D metabolism and action - addressing the skin as source and target. Nat Rev Endocrinol 2020. - PubMed

[6] Bikle D, Christakos S. New aspects of vitamin D metabolism and action - addressing the skin as source and target. Nat Rev Endocrinol 2020. - PubMed

[7] Bikle DD. Vitamin D receptor, UVR, and skin cancer: a potential protective mechanism. J Invest Dermatol 2008;128(10):2357–61. - PMC - PubMed

[8] Bikle DD. Vitamin D receptor, UVR, and skin cancer: a potential protective mechanism. J Invest Dermatol 2008;128(10):2357–61. - PMC - PubMed

[9] Bikle DD. The vitamin D receptor: a tumor suppressor in skin. Adv Exp Med Biol 2014;810:282–302. - PMC - PubMed

[10] Bikle DD. The vitamin D receptor: a tumor suppressor in skin. Adv Exp Med Biol 2014;810:282–302. - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin

Affiliations

Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin

Authors

Affiliations

Abstract

Conflict of interest statement

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous

Abstract

Conflict of interest statement

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous