Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice

    October 2008 in “ Endocrine reviews
    Roger Bouillon, Geert Carmeliet, Lieve Verlinden, Evelyne van Etten, Annemieke Verstuyf, Hilary F. Luderer, Liesbet Lieben, Chantal Mathieu, Marie B. Demay
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    TLDR Mice without the vitamin D receptor have bone issues and other health problems, suggesting vitamin D is important for preventing various diseases in humans.
    The document from 2008 discusses the importance of the vitamin D endocrine system, particularly the role of the vitamin D receptor (VDR) and its hormone, 1,25-dihydroxyvitamin D [1,25-(OH)2D], in maintaining calcium and bone homeostasis. Studies on mice with a deleted VDR gene revealed that the absence of VDR or the enzyme CYP27B1 results in bone abnormalities similar to those seen in humans with congenital diseases or severe vitamin D deficiency. The research highlighted that the intestine is a critical target for VDR action, as normal bone health can be restored with high calcium intake or selective VDR activation in the intestine. The VDR is expressed in many tissues, and the vitamin D system potentially regulates about 3% of the mouse or human genome. VDR-deficient mice develop total alopecia, which is not seen in mice deficient in vitamin D or 1α-hydroxylase, suggesting distinct roles for VDR and its ligand. While the immune system appears generally normal in VDR- or vitamin D-deficient mice, there is an increased susceptibility to autoimmune diseases. These mice also do not spontaneously develop cancer but are more susceptible to tumors when exposed to oncogenes or carcinogens. Additionally, they exhibit high renin hypertension, cardiac hypertrophy, and increased thrombogenicity. The findings suggest that vitamin D deficiency in humans may be linked to a higher prevalence of various diseases, and the paper calls for prospective studies on vitamin D supplementation to determine the benefits of maintaining optimal vitamin D levels.
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