The Steroid Vitamin D3 Reduces Cell Proliferation in Human Duodenal Epithelium

Abstract

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.

Inhibition of angiogenesis as a mechanism for inhibition by L?-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 of colon carcinogenesis induced by azoxymethane in Wistar rats

“…Thomas et al . (1997) examined the effect of 1,25(OH) 2 D 3 on human duodenal mucosal proliferation with an organ‐culture system combined with the metaphase arrest technique and found that 1,25(OH) 2 D 3 reduces median crypt cell production. Fife et al .…”

Inhibition of angiogenesis as a mechanism for inhibition by Lα‐hydroxyvitamin D3 and 1,25‐dihydroxyvitamin D3 of colon carcinogenesis induced by azoxymethane in Wistar rats

“…One is the effect of 1␣(OH)D 3 and 1,25(OH) 2 D 3 on cell proliferation. Thomas et al (1997) examined the effect of 1,25(OH) 2 D 3 on human duodenal mucosal proliferation with an organ-culture system combined with the metaphase arrest technique and found that 1,25(OH) 2 D 3 reduces median crypt cell production. Fife et al (1997) studied the effect of 1,25(OH) 2 D 3 on proliferation of human breast cancer cells, human prostate cancer cells and human osteosarcoma cells and found that it markedly inhibited cell proliferation and induced apoptosis in all 3 cell lines.…”

Age-related changes in the response of intestinal cells to 1α,25(OH)2-vitamin D3

“…1␣,25(OH) 2 D 3 regulates the proliferation and differentiation of several cell types (Abe et al, 1981;Farquahrson et al, 1993;Suda, 1989;Bikle and Pillai, 1993). The hormone also plays a role in the regulation of intestinal cells growth, reduced colonic (Thomas et al, 1992) and human duodenal (Thomas et al, 1997) mucosal cell proliferation have been seen in response to 1␣,25(OH) 2 D 3 . The hormone bound to VDR regulates the expression of more than 60 genes that exert pro-differentiation, antiproliferative and anti-metastatic effects.…”