Extrarenal sites of calcitriol synthesis: the particular role of the skin.

摘要: Calcitriol (1α,25(OH)2D3), the hormonally active form of vitamin D3(D3) is produced by a cascade reactions, including photochemical D3synthesis in skin and subsequent hydroxylation at C-25 atom liver finally C-1α position kidney. However, there substantial evidence for additional extrarenal sites calcitriol synthesis. In vitro, many nonrenal cells,including bone, placenta, prostata, keratinocytes, macrophages, T-lymphocytes several cancer cells (e.g., from lung, prostata skin) can enzymatically convert calcidiol (25OHD3) to 1a,25(OH)2D3. We have demonstrated that keratinocytes unique properties D3pathway; they are not only capable producing D3from 7-dehydrocholesterol (7-DHC), but also generate 1α,25(OH)2D3from substrates 25OHD3, 1a-hydroxyvitamin D3(1α-OHD3) even D3. It evident possess least 1α- OH-, 25OH- 24OHase activity, which necessary enzymatic conversion D3to 1α,25(OH)2D3, activity initiation catabolism 1α,25(OH)2D3to more polar metabolites. Thus, apparently tissue where complete UVB-induced pathway 7-DHC 1α,25(OH)2D3takes place under physiological circumstances.