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Stanniocalcin (STC) is an anti-hypercalcemic glycoprotein hormone previously identified in the corpuscles of Stannius in bony fish and recently in the human genome. This study undertook to express human STC in Chinese hamster ovary (CHO) cells and to determine its effects on calcium and phosphate absorption in swine and rat intestine. Unidirectional mucosal-to-serosal ( J m→s) and serosal-to-mucosal ( J s→m)45Ca and32P fluxes were measured in vitro in duodenal tissue in voltage-clamped Ussing chambers. Addition of STC (10–100 ng/ml) to the serosal surface of the duodenum resulted in a simultaneous increase in calcium J m→s and J s→mfluxes, with a subsequent reduction in net calcium absorption. This was coupled with an STC-stimulated increase in phosphate absorption. Intestinal conductance was increased at the highest dose of STC (100 ng/ml) in swine tissue. The addition of STC to the mucosal surface had no effect on calcium and phosphate fluxes. STC at doses of 10–1,000 ng/ml had no effect on short-circuit current in any region of the rat intestine. In conclusion, human recombinant STC decreases the absorption of calcium and stimulates the absorption of phosphate in both swine and rat duodenum. STC is a novel regulatory protein that regulates mammalian intestinal calcium and phosphate transport.

Previous studies have demonstrated that the resident bacteria harbored by interleukin (IL)-10 gene-deficient mice initiate an enterocolitis in the neonatal period. The associated intestinal injury is characterized by an increase in the secretion of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, and by a systemic response to endogenous bacterial antigens, supporting the hypothesis that a lack of tolerance may be the initiating cause. Whether bacterial initiation of this enterocolitis would occur in the adult intestine or whether it is only seen in the developing neonatal intestine was not known. Adult (9 weeks of age), axenic, luminally sterile IL-10 gene-deficient mice, which do not spontaneously develop enterocolitis, were inoculated with intestinal microbial flora. These mice rapidly developed intestinal injury and demonstrated elevated levels of IFN-gamma in cecal and colonic tissue. This response precedes a systemic spleen cell response to stimulation by bacterial antigens. Similarly, axenic, IL-10 gene-deficient mice exposed to microflora as neonates experience a comparable intestinal injury and IFN-gamma release before the appearance of IFN-gamma-producing cells in the spleen. Microbial colonization in control mice leads to systemic IL-10 production, but not systemic IFN-gamma production, suggesting that an IL-10-mediated suppression regulates the response in normal control mice but is absent in IL-10 gene-deficient mice. Our results suggest that the point at which intestinal microbial colonization occurs does not significantly influence the severity or specificity of the inflammatory response in IL-10 gene-deficient mice. The lack of tolerance to bacterial antigens appears to result from the absence of IL-10 during bacterial exposure.