Dermal fibroblasts pretreated with a sterol Delta7-reductase inhibitor produce 25-hydroxyvitamin D3 upon UVB irradiation

As dermis is a physiological site of vitamin D3 photoproduction, the photo-endocrine vitamin D3 system was studied in dermal fibroblasts. Dermal fibroblasts contain the vitamin D receptor and induce 1alpha,25-dihydroxyvitamin D3-24-hydroxylase [CYP24] mRNA upon stimulation with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. In addition, dermal fibroblasts contain mRNA of the vitamin D3-25-hydroxylases (CYP2R1 and CYP27A1). However, we could not detect any 25-hydroxyvitamin D3 [25OHD3]-1alpha-hydroxylase mRNA in dermal fibroblasts and no CYP24 mRNA was induced upon ultraviolet [UVB] irradiation, even when endogenous 7-dehydrocholesterol content was elevated by pretreatment with the sterol Delta7-reductase inhibitor BM15766. Nevertheless, dermal fibroblasts produce inactive vitamin D3 metabolites that can be activated by epidermal keratinocytes as CYP24 mRNA is induced in epidermal keratinocytes but not in dermal fibroblasts after transfer of medium or cellular suspensions from BM15766-pretreated, UVB-irradiated fibroblasts. This CYP24 induction was UVB-dose dependent and was inhibited by ketoconazole. As revealed in a competitive binding assay, BM15766-pretreated dermal fibroblasts are able to produce 25OHD3 upon UVB irradiation, but no 1,25(OH)2D3 was detected via combined high-performance liquid chromatography radioimmunoassay. The physiological relevance of dermal vitamin D3 photoproduction and its subsequent conversion into 25OHD3 remains elusive.status: publishe