Dermal fibroblasts pretreated with a sterol Δ7-reductase inhibitor produce 25-hydroxyvitamin D3 upon UVB irradiation

Abstract As dermis is a physiological site of vitamin D 3 photoproduction, the photo-endocrine vitamin D 3 system was studied in dermal fibroblasts. Dermal fibroblasts contain the vitamin D receptor and induce 1α,25-dihydroxyvitamin D 3 -24-hydroxylase [CYP24] mRNA upon stimulation with 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]. In addition, dermal fibroblasts contain mRNA of the vitamin D 3 -25-hydroxylases (CYP2R1 and CYP27A1). However, we could not detect any 25-hydroxyvitamin D 3 [25OHD 3 ]-1α-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 Δ 7 -reductase inhibitor BM15766. Nevertheless, dermal fibroblasts produce inactive vitamin D 3 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 25OHD 3 upon UVB irradiation, but no 1,25(OH) 2 D 3 was detected via combined high-performance liquid chromatography radioimmunoassay. The physiological relevance of dermal vitamin D 3 photoproduction and its subsequent conversion into 25OHD 3 remains elusive.