The steroid vitamin D3 reduces cell proliferation in human duodenal epithelium

1. The active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3, controls calcium absorption in the human duodenum, an effect that is mediated by mucosal vitamin D receptor expression. Functional vitamin D receptor signalling in the human colon is suggested by the reduced colonic mucosal cell proliferation seen in response to 1,25-dihydroxyvitamin D3. Thus 1,25-dihydroxyvitamin D3 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 D3 on human duodenal mucosal proliferation. To validate our technique, multiple human mucosal explants were established in organ culture and vincristine (0.6 micrograms/ml) was added at 10 h. Explants were removed sequentially from 10 to 15 h and metaphase arrest figures were demonstrated by using the Feulgen reaction. The mean number of metaphase arrest figures was plotted against time in culture to show a linear accumulation of metaphases between 11 and 15 h (correlation coefficient = 0.93, r2 = 0.87, P < 0.0001). The mean crypt cell production rate was 2.01 (0.27) cells/h per crypt. 3. Paired normal duodenal mucosal biopsies from six patients were then established in organ culture with or without 10(-10) mol/l (100 pmol/l) 1,25-dihydroxyvitamin D3. The crypt cell production rate was determined between 12 and 15 h after vincristine-induced metaphase arrest. 1,25-Dihydroxyvitamin D3 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 D3 reduces human duodenal epithelial cell proliferation.