1,25-Dihydroxyvitamin D3 production by human keratinocytes. Kinetics and regulation.

Human foreskin keratinocytes in vitro metabolize 25-hydroxy- vitamin D3 to a number of metabolites, including 1,25-dihy- droxyvitamin D3 (1,25(OH)2D3). This metabolite remains mostly within the cell and does not accumulate in the medium under the conditions of these experiments. With time, 1,25(OH)D3 is ca- tabolized, and more polar metabolites appear in both the cells and the medium. The production of 1,25(OH)D3 has an apparent Michaelis constant (K.) for 25-hydroxyvitamin D3 of 5.4 X 10-8 M. The levels of 1,25(OH)2D3 within the cell are increased both by increased production and decreased catabolism when para- thyroid hormone(1-34) and isobutylmethylxanthine are added. Exogenously added 1,25(OH)2D3 at concentrations as low as 10-12 M reduces endogenous 1,25(OH)D3 production, increases 1,25(OH)D3 catabolism, and increases 24,25-dihydroxyvitamin D3 production by an actinomycin D-sensitive process. These data indicate that the regulation of 1,25(OH)2D3 production by ker- atinocytes is similar to, but not identical to the regulation of 1,25(OH)2D3 by the kidney. (10, 11); anephric patients in one study had undetectable 1 ,25(OH)2D3 levels ( 12). Detectable levels ofthis metabolite were recently reported in an anephric patient with sarcoidosis (13), however, and in other anephric patients and anephric pigs given high doses of vitamin D (14, 15). Therefore, anephric humans