A Novel Pathway for Hormonally Active Calcitriol

Abstract

Calcitriol [1α,25(OH)<sub>2</sub>D<sub>3</sub>], the hormonally active form of vitamin D<sub>3</sub> (D<sub>3</sub>) is produced in both renal and extrarenal tissues. Our findings demonstrate that physiological doses of UVB radiation at 300 nm induce the conversion of 7-dehydrocholesterol (7-DHC) via preD<sub>3</sub> and D<sub>3</sub> into calcitriol in the pmol range in epidermal keratinocytes. The hydroxylation of photosynthesized D<sub>3</sub> to calcitriol is strongly suppressed by ketoconazole, a known inhibitor of cytochrome P450 mixed function oxidases. The UVB-induced formation of calcitriol in human skin is demonstrable in vivo by the microdialysis technique. These results suggest that human skin is an autonomous source of hormonally active calcitriol.