Department of Animal Science - Iowa State University

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Host:  Don Beitz

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“New Perspectives on Regulation by a Metabolite of Vitamin D”

25-Hydroxyvitamin D (25D) is best recognized as the metabolite used for clinical assessment of vitamin D status. Epidemiological studies have shown associations between various intestinal disorders, including calcium malabsorption, ulcerative colitis, Crohn’s disease, and colon cancer and low 25D concentrations in the blood. Oral supplementation with 25D has been effective in improving vitamin D status, but few studies have examined the immediate impact of oral 25D on the gut prior to absorption of 25D into circulation.

Recent investigations have shown that the intestines express the 1α-hydroxylase that may produce the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D). We hypothesized that orally consumed 25D can be locally activated for paracrine or autocrine action within the intestines to elicit a local vitamin D response. To test this hypothesis, we evaluated the duodenal response to 25D in mice through mRNA analyses, then developed in vitro conditions with human colon adenocarcinoma cell lines to characterize the mechanism driving the response.  Additionally, we investigated the potential response in the colon to glucuronide-modified 25D, a form of 25D found in bile.

In vivo results demonstrated a hormonal response to 25D that is similar to, but of lesser magnitude than that of 1,25D.  In vitro assays suggest that 25D elicits a response that is not affected by enzyme inhibition of 1α-hydroxylase and may imply a direct ligand effect of 25D.  These studies demonstrate that the colon and duodenum can respond to 25D that is within the lumen of the gut. This may provide a new mechanism for 25D to regulate calcium absorption in the intestines.