THE STEROID VITAMIN-D-3 REDUCES CELL-PROLIFERATION IN HUMAN DUODENAL EPITHELIUM

1. The active metabolite of vitamin D-3, 1,25-dihydroxyvitamin D-3, co ntrols calcium absorption in the human duodenum, an effect that is med iated by mucosal vitamin D receptor expression, Functional vitamin D r eceptor signalling in the human colon is suggested by the reduced colo nic mucosal cell proliferation seen in response to 1,25-dihydroxyvitam in D-3 Thus 1,25-dihydroxyvitamin D-3 might be expected to reduce cell proliferation in the small-bowel epithelium. 2. We have used an organ -culture system combined with the metaphase arrest technique to study the effects of 1,25-dihydroxyvitamin D-3 on human duodenal mucosal pro liferation. To validate our technique, multiple human organ added at 1 0 h, Explants were removed sequentially from 10 to 15 h and metaphase arrest figures were demonstrated by using the Feulgen reaction. The me an number of metaphase arrest figures was plotted against time in cult ure to show a linear accumulation of metaphases between 11 and 15 h (c orrelation coefficient = 0.93, r(2) = 0.87, P<0.0001), The mean crypt cell production rate was 2.01 (0.27) cells/h per crypt. 3. Paired norm al duodenal mucosal biopsies from six patients were then established i n organ culture with or without 10(-10) mol/l (100 pmol/l) 1,25-dihydr oxyvitamin D-3. The crypt cell production rate was determined between 12 and 15 h after vincristine-induced metaphase arrest. 1,25-Dihydroxy vitamin vitamin D-3 reduced the median crypt cell production rate from 2.42 (1.15-4.82) to 1.41 (0.03-2.05) cells/h per crypt (P<0.05), Thus , vitamin D-3 reduces human duodenal epithelial cell proliferation.