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• W2116742637 startingPage "3448" @default.
• W2116742637 abstract "20-Epi-1,25-dihydroxyvitamin D3 (20-epi-1,25(OH)2D3) is a vitamin D analog that exhibits unique biologic properties. The mechanism(s) responsible for these activities remains unclear. Here we explore the ability of 20-epi-1,25(OH)2D3 to induce calcemic responses in mice in vivo and identify a potential mechanism. Surprisingly, the levels of calcemia induced at 24 h after single injections of equivalent doses of 1,25(OH)2D3 or 20-epi-1,25(OH)2D3 were similar, suggesting that both compounds were equal in both potency and efficacy. This similarity was also observed at genes involved in calcium homeostasis including, S100g (calbindin D9K), Trpv6, Cldn2 (claudin 2), Trpv5, and Tnfsf11 (Rankl) as well as Cyp24a1. Despite this, the activities of the two compounds at 48 h were strikingly different. Thus, whereas the activity of 1,25-dihydroxyvitamin D3 declined at this time point, the response to 20-epi-1,25(OH)2D3 was increased. This unique profile was not due to an exaggerated induction of calcium regulating genes in the intestine, kidney, or bone but to a sustained action on these genes in the intestine. This conclusion was supported by studies using in vivo chromatin immunoprecipitation analysis, which revealed a prolonged presence of vitamin D receptor and RNA polymerase II at the Trpv6 and Cyp24a1 promoters and a sustained increase in histone 4 acetylation in these gene regions as well. We conclude that 20-epi-1,25(OH)2D3 displays superagonist properties largely as a result of its duration of action in the intestine. This action is likely due to a decrease in the rate of intestinal-specific degradation of the ligand rather than to an increase in the functional stability of the vitamin D receptor." @default.
• W2116742637 created "2016-06-24" @default.
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• W2116742637 date "2009-05-07" @default.
• W2116742637 modified "2023-10-07" @default.
• W2116742637 title "The Enhanced Hypercalcemic Response to 20-Epi-1,25-Dihydroxyvitamin D3 Results from a Selective and Prolonged Induction of Intestinal Calcium-Regulating Genes" @default.
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• W2116742637 doi "https://doi.org/10.1210/en.2009-0113" @default.
• W2116742637 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2717886" @default.
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• W2116742637 hasPublicationYear "2009" @default.
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