Parallel elevation of colonic 1,25-dihydroxyvitamin D3 levels and apoptosis in female mice on a calcium-deficient diet.

ABSTRACT

BACKGROUND: Epidemiology suggests that nutritional calcium and vitamin D together prevent colorectal tumor progression. 1,25(OH)2D3 is synthesized and degraded in colonocytes and, when bound to its receptor, has antiproliferative activity. MATERIALS AND METHODS: 1,25(OH)2D3 levels have been successfully measured in cell culture, but this is technically difficult in tissues. Double extraction coupled to an enzyme immunoassay was used to determine 1,25(OH)2D3 concentration in colon mucosa. RESULTS: In a mouse model fed low (0.04%) nutritional calcium, expression of the vitamin D catabolizing CYP24A1, of the synthesizing CYP27B1 hydroxylase and of the vitamin D receptor was induced in the right colon only. While CYP24A1 mRNA was raised in both genders, raised CYP27B1 and VDR was found in females only. Levels of 1,25(OH)2D3 were significantly higher in the right colon of females fed 0.04% calcium compared with the control group on 0.9% calcium, and with males fed either diet. Parallel to increased 1,25(OH)2D3, the intrinsic apoptotic pathway was enhanced in the right colon of females only. CONCLUSION: This demonstrates the significance of high nutritional calcium for colonic accumulation of 1,25(OH)2D3 and suggests that female sex hormones may protect against mitotic action of low nutritional calcium by inducing 1,25(OH)2D3 synthesis.