title: Bioactive forms of vitamin D selectively stimulate the skin analog of the hypothalamus-pituitary-adrenal axis in human epidermal keratinocytes.
abstract: Ultraviolet radiation B stimulates both the production of vitamin D3in the skin and the activation of the skin analog of the hypothalamic-pituitary-adrenal axis (HPA) as well as the central HPA. Since the role of vitamin D3in the regulation of the HPA is largely unknown, we investigated the impact of 1,25(OH)2D3and its noncalcemic analogs, 20(OH)D3and 21(OH)pD, on the expression of the local HPA in human epidermal keratinocytes. The noncalcemic analogs showed similar efficacy to 1,25(OH)2D3in stimulating the expression of neuropeptides, CRF, urocortins and POMC, and their receptors, CRFR1, CRFR2, MC1R, MC2R, MC3R and MC4R. Interestingly, unlike other secosteroids, the activity of 21(OH)pD did not correlate with induction of differentiation, suggesting a separate but overlapping mechanism of action. Thus, biologically active forms of vitamin D can regulate different elements of the local equivalent of the HPA with implications for the systemic HPA.
authors.affiliation: Department of Histology, Medical University of Gdańsk, Poland.
authors.forename: Justyna M
authors.initials: JM
authors.lastname: Wierzbicka
authors.affiliation: Department of Histology, Medical University of Gdańsk, Poland. Electronic address: mzmijewski@gumed.edu.pl.
authors.forename: Michał A
authors.initials: MA
authors.lastname: Żmijewski
authors.affiliation: Department of Histology, Medical University of Gdańsk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Piotrowska
authors.affiliation: Department and Clinic of Dermatology, Venereology and Allergology, Medical University of Gdansk, Poland.
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Nedoszytko
authors.affiliation: Department and Clinic of Dermatology, Venereology and Allergology, Medical University of Gdansk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Lange
authors.affiliation: School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Perth, WA 6009, Australia.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Tuckey
authors.affiliation: Department of Dermatology, University of Alabama Birmingham, Birmingham, AL 35294, USA; Comprehensive Cancer Center, Cancer Chemoprevention Program, University of Alabama Birmingham, Birmingham, AL 35294, USA; VA Medical Center, Birmingham, AL 35294, USA.
authors.forename: Andrzej T
authors.initials: AT
authors.lastname: Slominski
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D015153:Blotting, Western; D002118:Calcium / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology; D000078404:Epidermal Cells; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000166:cytology*; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000166:cytology*; D044103:Receptor, Melanocortin, Type 2 / Q000378:metabolism; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D044103:Receptor, Melanocortin, Type 2; D014807:Vitamin D; D002762:Cholecalciferol; D000324:Adrenocorticotropic Hormone; D002118:Calcium
keywords: Calcium; Corticotropin releasing factor; HPA axis; Keratinocytes differentiation; Vitamin D(3); Vitamin D(3) analogs