Vitamin D: Normal Function, Metabolism, Diseases, and Emerging Therapeutics

  • René St-Arnaud
  • Marie B. Demay
Part of the Topics in Bone Biology book series (TBB, volume 7)


Vitamin D is produced in the skin upon exposure to ultraviolet light (sunlight). It is activated in two steps to function as a key regulator of mineral ion homeostasis. Vitamin D becomes bound to the vitamin D binding protein, DBP, in the circulation and is transported to the liver where the enzyme vitamin D 25-hydroxylase (CYP2R1) adds a hydroxyl group on carbon 25 to produce 25-hydroxyvitamin D [25(OH)D]. When the 25(OH)D metabolite enters the bloodstream, it also becomes bound to DBP. In the kidney, it is further hydroxylated, gaining hormonal bioactivity. Hydroxylation at position 1α by the enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) converts 25(OH)D to 1α,25-dihydroxyvitamin D [1,25(OH)2D; calcitriol], the active, hormonal form of vitamin D. Upon reaching target tissues, 1,25(OH)2D binds to its specific receptor, the vitamin D receptor (VDR). This step enhances or inhibits the transcription of vitamin D target genes that carry out the physiological actions of 1,25(OH)2D: mineral homeostasis, skeletal homeostasis, and cellular differentiation.


Vitamin D Vitamin D hydroxylases Vitamin D receptor Rickets Cytochrome p450 enzymes 


  1. 1.
    Ahmad W, Faiyaz ul Haque M, Brancolini V, Tsou HC, ul Haque S, Lam H, Aita VM, Owen J, de Blaquiere M, Frank J, Cserhalmi-Friedman PB, Leask A, McGrath JA, Peacocke M, Ahmad M, Ott J, Christiano AM. Alopecia universalis associated with a mutation in the human hairless gene. Science. 1998;279:720–4.PubMedCrossRefGoogle Scholar
  2. 2.
    Aiba I, Yamasaki T, Shinki T, Izumi S, Yamamoto K, Yamada S, Terato H, Ide H, Ohyama Y. Characterization of rat and human CYP2J enzymes as vitamin D 25-hydroxylases. Steroids. 2006;71:849–56.PubMedCrossRefGoogle Scholar
  3. 3.
    Albertson DG, Ylstra B, Segraves R, Collins C, Dairkee SH, Kowbel D, Kuo WL, Gray JW, Pinkel D. Quantitative mapping of amplicon structure by array CGH identifies CYP24 as a candidate oncogene. Nat Genet. 2000;25:144–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Anderson MG, Nakane M, Ruan X, Kroeger PE, Wu-Wong JR. Expression of VDR and CYP24A1 mRNA in human tumors. Cancer Chemother Pharmacol. 2006;57:234–40.PubMedCrossRefGoogle Scholar
  5. 5.
    Andersson D, Davis DL, Dahlback H, Jornvall H. Cloning, structure and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J Biol Chem. 1989;264:8222–9.PubMedGoogle Scholar
  6. 6.
    Annalora AJ, Goodin DB, Hong WX, Zhang Q, Johnson EF, Stout CD. Crystal structure of CYP24A1, a mitochondrial cytochrome P450 involved in vitamin D metabolism. J Mol Biol. 2010;396:441–51.PubMedCrossRefGoogle Scholar
  7. 7.
    Arnaud C, Maijer R, Reade T, Scriver CR, Whelan DT. Vitamin D dependency: an inherited postnatal syndrome with secondary hyperparathyroidism. Pediatrics. 1970;46:871–80.PubMedGoogle Scholar
  8. 8.
    Baker AR, McDonnell DP, Hughes M, Crisp TM, Mangelsdorf DJ, Haussler MR, Pike JW, Shine J, O’Malley BW. Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci USA. 1988;85:3294–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Balsan S, Garabedian M, Larchet M, Gorski AM, Cournot G, Tau C, Bourdeau A, Silve C, Ricour C. Long-term nocturnal calcium infusions can cure rickets and promote normal mineralization in hereditary resistance to 1,25-dihydroxyvitamin D. J Clin Invest. 1986;77:1661–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Balsan S, Garabedian M, Liberman UA, Eil C, Bourdeau A, Guillozo H, Grimberg R, Le Deunff MJ, Lieberherr M, Guimbaud P, Broyer M, Marx SJ. Rickets and alopecia with resistance to 1,25-dihydroxyvitamin D: two different clinical courses with two different cellular defects. J Clin Endocrinol Metab. 1983;57:803–11.PubMedCrossRefGoogle Scholar
  11. 11.
    Balsan S, Garabedian M, Lieberherr M, Gueris J, Ulmann A, et al. Serum 1,25-dihydroxyvitamin D concentrations in two different types of pseudo-deficiency rickets. In: Norman AW, Schaefer K, Herrath DV, editors. Vitamin D: basic research and its clinical application. Berlin: Walter de Gruyter; 1979. p. 1143–9.Google Scholar
  12. 12.
    Bannister A, Kouzarides T. The CBP coactivator is a histone acetyl transferease. Nature. 1996;384:641–3.PubMedCrossRefGoogle Scholar
  13. 13.
    Barger-Lux MJ, Heaney RP. Effects of above average summer sun exposure on serum 25-hydroxyvitamin D and calcium absorption. J Clin Endocrinol Metab. 2002;87:4952–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Barsony J, Marx S. Rapid accumulation of cyclic GMP near activated vitamin D receptors. Proc Natl Acad Sci USA. 1991;88:1436–40.PubMedCrossRefGoogle Scholar
  15. 15.
    Barton DH, Hesse RH, Pechet MM, Rizzardo E. A convenient synthesis of 1-hydroxy-vitamin D 3. J Am Chem Soc. 1973;95:2748–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Benn BS, Ajibade D, Porta A, Dhawan P, Hediger M, Peng JB, Jiang Y, Oh GT, Jeung EB, Lieben L, Bouillon R, Carmeliet G, Christakos S. Active intestinal calcium transport in the absence of transient receptor potential vanilloid type 6 and calbindin-D9k. Endocrinology. 2008;149:3196–205.PubMedCrossRefGoogle Scholar
  17. 17.
    Binkley N, Ramamurthy R, Krueger D. Low vitamin D status: definition, prevalence, consequences, and correction. Endocrinol Metab Clin North Am. 2010;39:287–301. Table of contents.PubMedCrossRefGoogle Scholar
  18. 18.
    Bliziotes M, Yergey AL, Nanes MS, Muenzer J, Begley MG, Vieira NE, Kher KK, Brandi ML, Marx SJ. Absent intestinal response to calciferols in hereditary resistance to 1,25-dihydroxyvitamin D: documentation and effective therapy with high dose intravenous calcium infusions. J Clin Endocrinol Metab. 1988;66:294–300.PubMedCrossRefGoogle Scholar
  19. 19.
    Boehm MF, Fitzgerald P, Zou A, Elgort MG, Bischoff ED, Mere L, Mais DE, Bissonnette RP, Heyman RA, Nadzan AM, Reichman M, Allegretto EA. Novel ­nonsecosteroidal vitamin D mimics exert VDR-modulating activities with less calcium mobilization than 1,25-dihydroxyvitamin D3. Chem Biol. 1999;6:265–75.PubMedCrossRefGoogle Scholar
  20. 20.
    Bouillon R, Van Cromphaut S, Carmeliet G. Intestinal calcium absorption: molecular vitamin D mediated mechanisms. J Cell Biochem. 2003;88:332–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Boyan BD, Sylvia VL, McKinney N, Schwartz Z. Membrane actions of vitamin D metabolites 1alpha,25(OH)2D3 and 24R,25(OH)2D3 are retained in growth plate cartilage cells from vitamin D receptor knockout mice. J Cell Biochem. 2003;90:1207–23.PubMedCrossRefGoogle Scholar
  22. 22.
    Boyan BD, Wong KL, Wang L, Yao H, Guldberg RE, Drab M, Jo H, Schwartz Z. Regulation of growth plate chondrocytes by 1,25-dihydroxyvitamin D3 requires caveolae and caveolin-1. J Bone Miner Res. 2006;21:1637–47.PubMedCrossRefGoogle Scholar
  23. 23.
    Brooks MH, Bell NH, Love L, Stern PH, Orfei E, Queener SF, Hamstra AJ, DeLuca HF. Vitamin-D-dependent rickets type II. Resistance of target organs to 1,25-dihydroxyvitamin D. N Engl J Med. 1978;298:996–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Brown AJ, Slatopolsky E. Drug insight: vitamin D analogs in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. Nat Clin Pract Endocrinol Metab. 2007;3:134–44.PubMedCrossRefGoogle Scholar
  25. 25.
    Cali JJ, Hsieh CL, Francke U, Russell DW. Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. J Biol Chem. 1991;266:7779–83.PubMedGoogle Scholar
  26. 26.
    Cali JJ, Russell DW. Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reactions in bile acid biosynthesis. J Biol Chem. 1991;266:7774–8.PubMedGoogle Scholar
  27. 27.
    Calverley MJ. Synthesis of MC930, a biologically active vitamin D metabolite analogue. Tetrahedron. 1987;43:4609–19.CrossRefGoogle Scholar
  28. 28.
    Canadillas S, Rodriguez-Benot A, Rodriguez M. More on the bone-kidney axis – lessons from hypophosphataemia. Nephrol Dial Transplant. 2007;22:1521–3.PubMedCrossRefGoogle Scholar
  29. 29.
    Cao X, Ross FP, Zhang L, MacDonald PN, Chappel J, Teitelbaum SL. Cloning of the promoter for the avian integrin β3 subunit gene and its regulation by 1,25-dihydroxyvitamin D3. J Biol Chem. 1993;268:27371–80.PubMedGoogle Scholar
  30. 30.
    Casella SJ, Reiner BJ, Chen TC, Holick MF, Harrison HE. A possible genetic defect in 25-hydroxylation as a cause of rickets. J Pediatr. 1994;124:929–32.PubMedCrossRefGoogle Scholar
  31. 31.
    Castells S, Greig F, Fusi MA, Finberg L, Yasumura S, Liberman UA, Eil C, Marx SJ. Severely deficient binding of 1,25-dihydroxyvitamin D to its receptors in a patient responsive to high doses of this hormone. J Clin Endocrinol Metab. 1986;63:252–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Chen TL, Hirst MA, Cone CM, Hochberg Z, Tietze HU, Feldman D. 1,25-dihydroxyvitamin D ­resistance, rickets, and alopecia: analysis of receptors and ­bioresponse in cultured fibroblasts from patients and parents. J Clin Endocrinol Metab. 1984;59:383–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci USA. 2004;101:7711–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW. De-orphanization of Cytochrome P450 2R1: a microsomal vitamin D 25-hydroxylase. J Biol Chem. 2003;278:38084–93.PubMedCrossRefGoogle Scholar
  35. 35.
    Chiba N, Suldan Z, Freedman LP, Parvin J. Binding of liganded vitamin D receptor to the vitamin D receptor interacting protein coactivator complex induces interaction with RNA polymerase II holoenzyme. J Biol Chem. 2000;275:10719–22.PubMedCrossRefGoogle Scholar
  36. 36.
    Chung I, Karpf AR, Muindi JR, Conroy JM, Nowak NJ, Johnson CS, Trump DL. Epigenetic silencing of CYP24 in tumor-derived endothelial cells contributes to selective growth inhibition by calcitriol. J Biol Chem. 2007;282:8704–14.PubMedCrossRefGoogle Scholar
  37. 37.
    Cianferotti L, Cox M, Skorija K, Demay MB. Vitamin D receptor is essential for normal keratinocyte stem cell function. Proc Natl Acad Sci USA. 2007;104:9428–33.PubMedCrossRefGoogle Scholar
  38. 38.
    Civitelli R, Kim YS, Gunsten SL, Fujimori A, Huskey M, Avioli LV, Hruska KA. Nongenomic activation of the calcium message system by vitamin D metabolites in osteoblast-like cells. Endocrinology. 1990;127:2253–62.PubMedCrossRefGoogle Scholar
  39. 39.
    Cross HS, Bises G, Lechner D, Manhardt T, Kallay E. The vitamin D endocrine system of the gut – its possible role in colorectal cancer prevention. J Steroid Biochem Mol Biol. 2005;97:121–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Cross HS, Kallay E, Lechner D, Gerdenitsch W, Adlercreutz H, Armbrecht HJ. Phytoestrogens and vitamin D metabolism: a new concept for the prevention and therapy of colorectal, prostate, and mammary carcinomas. J Nutr. 2004;134:1207S–12.PubMedGoogle Scholar
  41. 41.
    Dardenne O, Prud’homme J, Arabian A, Glorieux FH, St-Arnaud R. Targeted inactivation of the 25-hydroxy­vitamin D(3)-1(alpha)- hydroxylase gene (CYP27B1) creates an animal model of pseudovitamin D- deficiency rickets. Endocrinology. 2001;142:3135–41.PubMedCrossRefGoogle Scholar
  42. 42.
    Dardenne O, Prud’homme J, Hacking SA, Glorieux FH, St-Arnaud R. Correction of the abnormal mineral ion homeostasis with a high-calcium, high-phosphorus, high-lactose diet rescues the PDDR pheno­type of mice deficient for the 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1). Bone. 2003;32:332–40.PubMedCrossRefGoogle Scholar
  43. 43.
    Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16:713–6.PubMedCrossRefGoogle Scholar
  44. 44.
    de Boland AR, Nemere I, Norman AW. Ca2+-Channel agonist bay K8644 mimics 1,25(OH)2-vitamin D3 rapid enhancement of Ca2+ transport in chick perfused duodenum. Biochem Biophys Res Commun. 1990;166:217–22.PubMedCrossRefGoogle Scholar
  45. 45.
    Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer. 2007;7:684–700.PubMedCrossRefGoogle Scholar
  46. 46.
    DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004;80:1689S–96.PubMedGoogle Scholar
  47. 47.
    Delvin EE, Glorieux FH, Marie PJ, Pettifor JM. Vitamin D dependency: replacement therapy with calcitriol. J Pediatr. 1981;99:26–34.PubMedCrossRefGoogle Scholar
  48. 48.
    Demay MB, Gerardi JM, DeLuca HF, Kronenberg HM. DNA sequences in the rat osteocalcin gene that bind the 1,25-dihydroxyvitamin D3 receptor and confer responsiveness to 1,25-dihydroxyvitamin D3. Proc Natl Acad Sci USA. 1990;87:369–73.PubMedCrossRefGoogle Scholar
  49. 49.
    Demay MB, Kiernan MS, DeLuca HF, Kronenberg HM. Characterization of 1,25-dihydroxyvitamin D3 receptor interactions with target sequences in the rat osteocalcin gene. Mol Endocrinol. 1992;6:557–62.PubMedCrossRefGoogle Scholar
  50. 50.
    Dong LM, Ulrich CM, Hsu L, Duggan DJ, Benitez DS, White E, Slattery ML, Farin FM, Makar KW, Carlson CS, Caan BJ, Potter JD, Peters U. Vitamin D related genes, CYP24A1 and CYP27B1, and colon cancer risk. Cancer Epidemiol Biomarkers Prev. 2009;18:2540–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Drueke TB. Which vitamin D derivative to prescribe for renal patients. Curr Opin Nephrol Hypertens. 2005;14:343–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Elder G. Pathophysiology and recent advances in the management of renal osteodystrophy. J Bone Miner Res. 2002;17:2094–105.PubMedCrossRefGoogle Scholar
  53. 53.
    Erben RG, Soegiarto DW, Weber K, Zeitz U, Lieberherr M, Gniadecki R, Moller G, Adamski J, Balling R. Deletion of deoxyribonucleic acid binding domain of the vitamin D receptor abrogates genomic and nongenomic functions of vitamin D. Mol Endocrinol. 2002;16:1524–37.PubMedCrossRefGoogle Scholar
  54. 54.
    Farach-Carson MC, Sergeev I, Norman AW. Nongenomic actions of 1,25-dihydroxyvitamin D3 in rat osteosarcoma cells: structure-function studies using ligand analogs. Endocrinology. 1991;129:1876–84.PubMedCrossRefGoogle Scholar
  55. 55.
    Farhan H, Cross HS. Transcriptional inhibition of CYP24 by genistein. Ann N Y Acad Sci. 2002;973:459–62.PubMedCrossRefGoogle Scholar
  56. 56.
    Farhan H, Wahala K, Adlercreutz H, Cross HS. Isoflavonoids inhibit catabolism of vitamin D in prostate cancer cells. J Chromatogr B Analyt Technol Biomed Life Sci. 2002;777:261–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Farhan H, Wahala K, Cross HS. Genistein inhibits vitamin D hydroxylases CYP24 and CYP27B1 expression in prostate cells. J Steroid Biochem Mol Biol. 2003;84:423–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Fraser D, Kooh SW, Kind HP, Holick MF, Tanaka Y, DeLuca HF. Pathogenesis of hereditary vitamin-D-dependent rickets. An inborn error of vitamin D metabolism involving defective conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D. N Engl J Med. 1973;289:817–22.PubMedCrossRefGoogle Scholar
  59. 59.
    Frazao JM, Chesney RW, Coburn JW. Intermittent oral 1alpha-hydroxyvitamin D2 is effective and safe for the suppression of secondary hyperparathyroidism in haemodialysis patients. 1alphaD2 Study Group. Nephrol Dial Transplant. 1998;13 Suppl 3:68–72.PubMedCrossRefGoogle Scholar
  60. 60.
    Frazao JM, Elangovan L, Maung HM, Chesney RW, Acchiardo SR, Bower JD, Kelley BJ, Rodriguez HJ, Norris KC, Robertson JA, Levine BS, Goodman WG, Gentile D, Mazess RB, Kyllo DM, Douglass LL, Bishop CW, Coburn JW. Intermittent doxercalciferol (1alpha-hydroxyvitamin D(2)) therapy for secondary hyperparathyroidism. Am J Kidney Dis. 2000;36:550–61.PubMedCrossRefGoogle Scholar
  61. 61.
    Fu GK, Lin D, Zhang MY, Bikle DD, Shackleton CH, Miller WL, Portale AA. Cloning of human 25-hydroxyvitamin D-1 alpha-hydroxylase and mutations causing vitamin D-dependent rickets type 1. Mol Endocrinol. 1997;11:1961–70.PubMedCrossRefGoogle Scholar
  62. 62.
    Fu GK, Portale AA, Miller WL. Complete structure of the human gene for the vitamin D 1alpha- hydroxylase, P450c1alpha. DNA Cell Biol. 1997;16:1499–507.PubMedCrossRefGoogle Scholar
  63. 63.
    Fujita H, Sugimoto K, Inatomi S, Maeda T, Osanai M, Uchiyama Y, Yamamoto Y, Wada T, Kojima T, Yokozaki H, Yamashita T, Kato S, Sawada N, Chiba H. Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. Mol Biol Cell. 2008;19:1912–21.PubMedCrossRefGoogle Scholar
  64. 64.
    Fukushige S, Waldman FM, Kimura M, Abe T, Furukawa T, Sunamura M, Kobari M, Horii A. Frequent gain of copy number on the long arm of chromosome 20 in human pancreatic adenocarcinoma. Genes Chromosomes Cancer. 1997;19:161–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Fukushima M, Suzuki Y, Tohira Y, Nishii Y, Suzuki M. 25-Hydroxylation of 1alpha-hydroxyvitamin D3 in vivo and in perfused rat liver. FEBS Lett. 1976;65:211–4.PubMedCrossRefGoogle Scholar
  66. 66.
    Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 1980;9:227–31.PubMedCrossRefGoogle Scholar
  67. 67.
    Ginde AA, Liu MC, Camargo Jr CA. Demographic differences and trends of vitamin D insufficiency in the US population, 1988–2004. Arch Intern Med. 2009;169:626–32.PubMedCrossRefGoogle Scholar
  68. 68.
    Glorieux FH. Calcitriol treatment in vitamin D-dependent and vitamin D-resistant rickets. Metabolism. 1990;39(suppl):10–2.PubMedCrossRefGoogle Scholar
  69. 69.
    Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 2005;19:1067–77.PubMedCrossRefGoogle Scholar
  70. 70.
    Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, Elashoff RM, Salusky IB. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med. 2000;342:1478–83.PubMedCrossRefGoogle Scholar
  71. 71.
    Gupta RP, Hollis BW, Patel SB, Bell NH. CYP3A4 is a human microsomal vitamin D-25-hydroxylase. J Bone Miner Res. 2004;19(4):680–8. Epub 2003.PubMedCrossRefGoogle Scholar
  72. 72.
    Hahn CN, Baker E, Laslo P, May BK, Omdahl JL, Sutherland GR. Localization of the human vitamin D 24-hydroxylase gene (CYP24) to chromosome 20q13.2->q13.3. Cytogenet Cell Genet. 1993;62:192–3.PubMedCrossRefGoogle Scholar
  73. 73.
    Haussler MR, Haussler CA, Bartik L, Whitfield GK, Hsieh JC, Slater S, Jurutka PW. Vitamin D receptor: molecular signaling and actions of nutritional ligands in disease prevention. Nutr Rev. 2008;66:S98–112.PubMedCrossRefGoogle Scholar
  74. 74.
    Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, Dominguez CE, Jurutka PW. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res. 1998;13:325–49.PubMedCrossRefGoogle Scholar
  75. 75.
    Heaney RP, Armas LA, Shary JR, Bell NH, Binkley N, Hollis BW. 25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions. Am J Clin Nutr. 2008;87:1738–42.PubMedGoogle Scholar
  76. 76.
    Helvig C, Kharebov A, Petkovich M, Ryder K, Ireland B, Cuerrier D. The role of CYP24-mediated catabolism on vitamin D status and responsiveness in a rodent model of CKD. J Bone Miner Res. 2009. Vol 24 (Suppl. 1): Available at URL:
  77. 77.
    Hendrich B, Hardeland U, Ng HH, Jiricny J, Bird A. The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites. Nature. 1999;401:301–4.PubMedCrossRefGoogle Scholar
  78. 78.
    Hirst MA, Hochman HI, Feldman D. Vitamin D resistance and alopecia: a kindred with normal 1,25-dihydroxyvitamin D binding, but decreased receptor affinity for deoxyribonucleic acid. J Clin Endocrinol Metab. 1985;60:490–5.PubMedCrossRefGoogle Scholar
  79. 79.
    Hochberg Z, Benderli A, Levy J, Vardi P, Weisman Y, Chen T, Feldman D. 1,25-Dihydroxyvitamin D resistance, rickets, and alopecia. Am J Med. 1984;77:805–11.PubMedCrossRefGoogle Scholar
  80. 80.
    Hochberg Z, Tiosano D, Even L. Calcium therapy for calcitriol-resistant rickets. J Pediatr. 1992;121:803–8.PubMedCrossRefGoogle Scholar
  81. 81.
    Hodgson G, Hager JH, Volik S, Hariono S, Wernick M, Moore D, Nowak N, Albertson DG, Pinkel D, Collins C, Hanahan D, Gray JW. Genome scanning with array CGH delineates regional alterations in mouse islet carcinomas. Nat Genet. 2001;29:459–64.PubMedCrossRefGoogle Scholar
  82. 82.
    Hoenderop J, VanDerKemp A, Hartog A, VandeGraaf S, Van Os C, Willems P, Bindels R. Molecular identification of the apical Ca2+ channel in 1,25-dihydroxyvitamin D-responsive epithelia. J Biol Chem. 1999;274:8375–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Hoenderop JG, van Leeuwen JP, van der Eerden BC, Kersten FF, van der Kemp AW, Merillat AM, Waarsing JH, Rossier BC, Vallon V, Hummler E, Bindels RJ. Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5. J Clin Invest. 2003;112:1906–14.PubMedGoogle Scholar
  84. 84.
    Hofmann AF. Detoxification of lithocholic acid, a toxic bile acid: relevance to drug hepatotoxicity. Drug Metab Rev. 2004;36:703–22.PubMedCrossRefGoogle Scholar
  85. 85.
    Holick CN, Stanford JL, Kwon EM, Ostrander EA, Nejentsev S, Peters U. Comprehensive association analysis of the vitamin D pathway genes, VDR, CYP27B1, and CYP24A1, in prostate cancer. Cancer Epidemiol Biomarkers Prev. 2007;16:1990–9.PubMedCrossRefGoogle Scholar
  86. 86.
    Holick MF. Photobiology of vitamin D. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press; 1997. p. 33–9.Google Scholar
  87. 87.
    Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, Petruschke RA, Chen E, de Papp AE. Prevalence of vitamin D inadequacy among ­postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab. 2005;90:3215–24.PubMedCrossRefGoogle Scholar
  88. 88.
    Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005;135:317–22.PubMedGoogle Scholar
  89. 89.
    Hollis BW. Assessment and interpretation of circulating 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in the clinical environment. Endocrinol Metab Clin North Am. 2010;39:271–86. Table of contents.PubMedCrossRefGoogle Scholar
  90. 90.
    Hosseinpour F, Ibranovic I, Tang W, Wikvall K. 25-Hydroxylation of vitamin D3 in primary cultures of pig hepatocytes: evidence for a role of both CYP2D25 and CYP27A1. Biochem Biophys Res Commun. 2003;303:877–83.PubMedCrossRefGoogle Scholar
  91. 91.
    Hsieh JC, Sisk JM, Jurutka PW, Haussler CA, Slater SA, Haussler MR, Thompson CC. Physical and functional interaction between the vitamin D receptor and hairless corepressor, two proteins required for hair cycling. J Biol Chem. 2003;278:38665–74.PubMedCrossRefGoogle Scholar
  92. 92.
    Hughes MR, Malloy PJ, Kieback DG, Kesterson RA, Pike JW, Feldman D, O’Malley BW. Point mutations in the human vitamin D receptor gene associated with hypocalcemic rickets. Science. 1988;242:1702–5.PubMedCrossRefGoogle Scholar
  93. 93.
    Ingram D, Sanders K, Kolybaba M, Lopez D. Case-control study of phyto-oestrogens and breast cancer. Lancet. 1997;350:990–4.PubMedCrossRefGoogle Scholar
  94. 94.
    Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board and Institute of Medicine Staff. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, D.C.: National Academy Press; 1997.Google Scholar
  95. 95.
    Ishizuka S, Kurihara N, Reddy SV, Cornish J, Cundy T, Roodman GD. (23S)-25-Dehydro-1{alpha}-hydroxyvitamin D3–26,23-lactone, a vitamin D receptor antagonist that inhibits osteoclast formation and bone resorption in bone marrow cultures from patients with Paget’s disease. Endocrinology. 2005;146:2023–30.PubMedCrossRefGoogle Scholar
  96. 96.
    Jacobsen BK, Knutsen SF, Fraser GE. Does high soy milk intake reduce prostate cancer incidence? The Adventist Health Study (United States). Cancer Causes Control. 1998;9:553–7.PubMedCrossRefGoogle Scholar
  97. 97.
    Jones G. Vitamin D analogs. Endocrinol Metab Clin North Am. 2010;39:447–72. Table of contents.PubMedCrossRefGoogle Scholar
  98. 98.
    Jones G, Ramshaw H, Zhang A, Cook R, Byford V, White J, Petkovich M. Expression and activity of ­vitamin D-metabolizing cytochrome P450s (CYP1alpha and CYP24) in human nonsmall cell lung carcinomas. Endocrinology. 1999;140:3303–10.PubMedCrossRefGoogle Scholar
  99. 99.
    Kahraman M, Sinishtaj S, Dolan PM, Kensler TW, Peleg S, Saha U, Chuang SS, Bernstein G, Korczak B, Posner GH. Potent, selective and low-calcemic inhibitors of CYP24 hydroxylase: 24-sulfoximine analogues of the hormone 1alpha,25-dihydroxyvitamin D(3). J Med Chem. 2004;47:6854–63.PubMedCrossRefGoogle Scholar
  100. 100.
    Kallay E, Adlercreutz H, Farhan H, Lechner D, Bajna E, Gerdenitsch W, Campbell M, Cross HS. Phytoestrogens regulate vitamin D metabolism in the mouse colon: relevance for colon tumor prevention and therapy. J Nutr. 2002;132:3490S–3.PubMedGoogle Scholar
  101. 101.
    Kerry DM, Dwivedi PP, Hahn CN, Morris HA, Omdahl JL, May BK. Transcriptional synergism between vitamin D-responsive elements in the rat 25-hydroxyvitamin D3 24-hydroxylase (CYP24) promoter. J Biol Chem. 1996;271:29715–21.PubMedCrossRefGoogle Scholar
  102. 102.
    Khanal RC, Nemere I. The ERp57/GRp58/1,25D3-MARRS receptor: multiple functional roles in diverse cell systems. Curr Med Chem. 2007;14:1087–93.PubMedCrossRefGoogle Scholar
  103. 103.
    Kim CJ, Kaplan LE, Perwad F, Huang N, Sharma A, Choi Y, Miller WL, Portale AA. Vitamin D 1alpha-hydroxylase gene mutations in patients with 1alpha-hydroxylase deficiency. J Clin Endocrinol Metab. 2007;92:3177–82.PubMedCrossRefGoogle Scholar
  104. 104.
    Kim MS, Fujiki R, Murayama A, Kitagawa H, Yamaoka K, Yamamoto Y, Mihara M, Takeyama K, Kato S. 1Alpha,25(OH)2D3-induced transrepression by vitamin D receptor through E-box-type elements in the human parathyroid hormone gene promoter. Mol Endocrinol. 2007;21:334–42.PubMedCrossRefGoogle Scholar
  105. 105.
    Kim MS, Kondo T, Takada I, Youn MY, Yamamoto Y, Takahashi S, Matsumoto T, Fujiyama S, Shirode Y, Yamaoka I, Kitagawa H, Takeyama K, Shibuya H, Ohtake F, Kato S. DNA demethylation in hormone-induced transcriptional derepression. Nature. 2009;461:1007–12.PubMedCrossRefGoogle Scholar
  106. 106.
    Kitada H, Miyata M, Nakamura T, Tozawa A, Honma W, Shimada M, Nagata K, Sinal CJ, Guo GL, Gonzalez FJ, Yamazoe Y. Protective role of hydroxysteroid sulfotransferase in lithocholic acid-induced liver toxicity. J Biol Chem. 2003;278:17838–44.PubMedCrossRefGoogle Scholar
  107. 107.
    Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S. The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. Cell. 2003;113:905–17.PubMedCrossRefGoogle Scholar
  108. 108.
    Kitanaka S, Murayama A, Sakaki T, Inouye K, Seino Y, Fukumoto S, Shima M, Yukizane S, Takayanagi M, Niimi H, Takeyama K, Kato S. No enzyme activity of 25-hydroxyvitamin D3 1alpha-hydroxylase gene product in pseudovitamin D deficiency rickets, including that with mild clinical manifestation. J Clin Endocrinol Metab. 1999;84:4111–7.PubMedCrossRefGoogle Scholar
  109. 109.
    Kitanaka S, Takeyama K, Murayama A, Sato T, Okumura K, Nogami M, Hasegawa Y, Niimi H, Yanagisawa J, Tanaka T, Kato S. Inactivating ­mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficiency rickets. N Engl J Med. 1998;338:653–61.PubMedCrossRefGoogle Scholar
  110. 110.
    Korn WM, Yasutake T, Kuo WL, Warren RS, Collins C, Tomita M, Gray J, Waldman FM. Chromosome arm 20q gains and other genomic alterations in colorectal cancer metastatic to liver, as analyzed by comparative genomic hybridization and fluorescence in situ hybridization. Genes Chromosomes Cancer. 1999;25:82–90.PubMedCrossRefGoogle Scholar
  111. 111.
    Kragballe K, Gjertsen BT, De Hoop D, Karlsmark T, van de Kerkhof PC, Larko O, Nieboer C, Roed-Petersen J, Strand A, Tikjob G. Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris. Lancet. 1991;337:193–6.PubMedCrossRefGoogle Scholar
  112. 112.
    Kraichely D, Collins J, DeLisle R, MacDonald PN. The autonomous transactivation domain in helix H3 of the vitamin D receptor is required for transactivation and coactivator interaction. J Biol Chem. 1999;274:14352–8.PubMedCrossRefGoogle Scholar
  113. 113.
    Kudoh T, Kumagai T, Uetsuji N, Tsugawa S, Oyanagi K, Chiba Y, Minami R, Nakao T. Vitamin D dependent rickets: decreased sensitivity to 1,25-dihydroxyvitamin D. Eur J Pediatr. 1981;137:307–11.PubMedCrossRefGoogle Scholar
  114. 114.
    Kuriyama M, Fujiyama J, Kubota R, Nakagawa M, Osame M. Osteoporosis and increased bone fractures in cerebrotendinous xanthomatosis. Metabolism. 1993;42:1497–8.PubMedCrossRefGoogle Scholar
  115. 115.
    Labuda M, Labuda D, Korab-Laskowska M, Cole DE, Zietkiewicz E, Weissenbach J, Popowska E, Pronicka E, Root AW, Glorieux FH. Linkage disequilibrium analysis in young populations: pseudo-vitamin D-deficiency rickets and the founder effect in French Canadians. Am J Hum Genet. 1996;59:633–43.PubMedGoogle Scholar
  116. 116.
    Labuda M, Morgan K, Glorieux FH. Mapping autosomal recessive vitamin D dependency type I to chromosome 12q14 by linkage analysis. Am J Hum Genet. 1990;47:28–36.PubMedGoogle Scholar
  117. 117.
    Li YC, Amling M, Pirro AE, Priemel M, Meuse J, Baron R, Delling G, Demay MB. Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice. Endocrinology. 1998;139:4391–6.PubMedCrossRefGoogle Scholar
  118. 118.
    Li YC, Bergwitz C, Juppner H, Demay M. Cloning and characterization of the vitamin D receptor from Xenopus laevis. Endocrinology. 1997;138:2347–53.PubMedCrossRefGoogle Scholar
  119. 119.
    Lips P, Hosking D, Lippuner K, Norquist JM, Wehren L, Maalouf G, Ragi-Eis S, Chandler J. The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J Intern Med. 2006;260:245–54.PubMedCrossRefGoogle Scholar
  120. 120.
    Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zugel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770–3.PubMedCrossRefGoogle Scholar
  121. 121.
    Liu S, Gupta A, Quarles LD. Emerging role of fibroblast growth factor 23 in a bone-kidney axis regulating systemic phosphate homeostasis and extracellular matrix mineralization. Curr Opin Nephrol Hypertens. 2007;16:329–35.PubMedCrossRefGoogle Scholar
  122. 122.
    Llach F, Fernandez E. Overview of renal bone disease: causes of treatment failure, clinical observations, the changing pattern of bone lesions, and future therapeutic approach. Kidney Int. 2003;64(Suppl):S113–9.CrossRefGoogle Scholar
  123. 123.
    Loose DS, Kan PB, Hirst MA, Marcus RA, Feldman D. Ketoconazole blocks adrenal steroidogenesis by inhibiting cytochrome P450-dependent enzymes. J Clin Invest. 1983;71:1495–9.PubMedCrossRefGoogle Scholar
  124. 124.
    Lou YR, Qiao S, Talonpoika R, Syvala H, Tuohimaa P. The role of vitamin D3 metabolism in prostate cancer. J Steroid Biochem Mol Biol. 2004;92:317–25.PubMedCrossRefGoogle Scholar
  125. 125.
    Ma Y, Khalifa B, Yee YK, Lu J, Memezawa A, Savkur RS, Yamamoto Y, Chintalacharuvu SR, Yamaoka K, Stayrook KR, Bramlett KS, Zeng QQ, Chandrasekhar S, Yu XP, Linebarger JH, Iturria SJ, Burris TP, Kato S, Chin WW, Nagpal S. Identification and characterization of noncalcemic, tissue-selective, nonsecosteroidal vitamin D receptor modulators. J Clin Invest. 2006;116:892–904.PubMedCrossRefGoogle Scholar
  126. 126.
    Makin G, Lohnes D, Byford V, Ray R, Jones G. Target cell metabolism of 1,25-dihydroxyvitamin D3 to calcitroic acid. Evidence for a pathway in kidney and bone involving 24-oxidation. Biochem J. 1989;262:173–80.PubMedGoogle Scholar
  127. 127.
    Makishima M, Lu TT, Xie W, Whitfield GK, Domoto H, Evans RM, Haussler MR, Mangelsdorf DJ. Vitamin D receptor as an intestinal bile acid sensor. Science. 2002;296:1313–6.PubMedCrossRefGoogle Scholar
  128. 128.
    Malas S, Peters J, Abbott C. The genes for endothelin 3, vitamin D 24-hydroxylase, and melanocortin 3 receptor map to distal mouse chromosome 2, in the region of conserved synteny with human chromosome 20. Mamm Genome. 1994;5:577–9.PubMedCrossRefGoogle Scholar
  129. 129.
    Malloy PJ, Eccleshall TR, Gross C, Van Maldergem L, Bouillon R, Feldman D. Hereditary vitamin D resistant rickets caused by a novel mutation in the vitamin D receptor that results in decreased affinity for hormone and cellular hyporesponsiveness. J Clin Invest. 1997;99:297–304.PubMedCrossRefGoogle Scholar
  130. 130.
    Malloy PJ, Feldman D. Genetic disorders and defects in vitamin d action. Endocrinol Metab Clin North Am. 2010;39:333–46. Table of contents.PubMedCrossRefGoogle Scholar
  131. 131.
    Malloy PJ, Hochberg Z, Tiosano D, Pike JW, Hughes MR, Feldman D. The molecular basis of hereditary 1,25-dihydroxyvitamin D3 resistant rickets in seven related families. J Clin Invest. 1990;86:2071–9.PubMedCrossRefGoogle Scholar
  132. 132.
    Malloy PJ, Pike JW, Feldman D. The vitamin D receptor and the syndrome of hereditary 1,25- dihydroxyvitamin D-resistant rickets. Endocr Rev. 1999;20:156–88.PubMedCrossRefGoogle Scholar
  133. 133.
    Martin KJ, Gonzalez EA, Gellens M, Hamm LL, Abboud H, Lindberg J. 19-Nor-1-alpha-25-dihydroxyvitamin D2 (Paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis. J Am Soc Nephrol. 1998;9:1427–32.PubMedGoogle Scholar
  134. 134.
    Martinez I, Saracho R, Montenegro J, Llach F. The importance of dietary calcium and phosphorous in the secondary hyperparathyroidism of patients with early renal failure. Am J Kidney Dis. 1997;29:496–502.PubMedCrossRefGoogle Scholar
  135. 135.
    Marx SJ, Bliziotes MM, Nanes M. Analysis of the relation between alopecia and resistance to 1,25-dihydroxyvitamin D. Clin Endocrinol. 1986;25:373–81.CrossRefGoogle Scholar
  136. 136.
    Marx SJ, Spiegel AM, Brown EM, Gardner DG, Downs Jr RW, Attie M, Hamstra AJ, DeLuca HF. A familial syndrome of decrease in sensitivity to 1,25-dihydroxyvitamin D. J Clin Endocrinol Metab. 1978;47:1303–10.PubMedCrossRefGoogle Scholar
  137. 137.
    Masuda S, Strugnell S, Calverley MJ, Makin HL, Kremer R, Jones G. In vitro metabolism of the anti-psoriatic vitamin D analog, calcipotriol, in two cultured human keratinocyte models. J Biol Chem. 1994;269:4794–803.PubMedGoogle Scholar
  138. 138.
    Masuyama R, Stockmans I, Torrekens S, Van Looveren R, Maes C, Carmeliet P, Bouillon R, Carmeliet G. Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts. J Clin Invest. 2006;116:3150–9.PubMedCrossRefGoogle Scholar
  139. 139.
    Maung HM, Elangovan L, Frazao JM, Bower JD, Kelley BJ, Acchiardo SR, Rodriguez HJ, Norris KC, Sigala JF, Rutkowski M, Robertson JA, Goodman WG, Levine BS, Chesney RW, Mazess RB, Kyllo DM, Douglass LL, Bishop CW, Coburn JW. Efficacy and side effects of intermittent intravenous and oral doxercalciferol (1alpha-hydroxyvitamin D(2)) in dialysis patients with secondary hyperparathyroidism: a sequential comparison. Am J Kidney Dis. 2001;37:532–43.PubMedCrossRefGoogle Scholar
  140. 140.
    McCullough ML, Bostick RM, Mayo TL. Vitamin D gene pathway polymorphisms and risk of colorectal, breast, and prostate cancer. Annu Rev Nutr. 2009;29:111–32.PubMedCrossRefGoogle Scholar
  141. 141.
    McKenna N, Xu J, Nawaz Z, Tsai S, Tsai M, O’Malley B. Nuclear receptor coactivators: multiple enzymes, multiple complexes, multiple functions. J Steroid Biochem Molec Biol. 1999;69:3–12.PubMedCrossRefGoogle Scholar
  142. 142.
    Medhora MM, Teitelbaum S, Chappel J, Alvarez J, Mimura H, Ross FP, Hruska K. 1α,25-dihydroxyvitamin D3 up-regulates expression of the osteoclast integrin αvβ3. J Biol Chem. 1993;268:1456–61.PubMedGoogle Scholar
  143. 143.
    Meijer GA, Hermsen MA, Baak JP, van Diest PJ, Meuwissen SG, Belien JA, Hoovers JM, Joenje H, Snijders PJ, Walboomers JM. Progression from colorectal adenoma to carcinoma is associated with non-random chromosomal gains as detected by comparative genomic hybridisation. J Clin Pathol. 1998;51:901–9.PubMedCrossRefGoogle Scholar
  144. 144.
    Meyer MB, Goetsch PD, Pike JW. A downstream intergenic cluster of regulatory enhancers ­contributes to the induction of CYP24A1 expression by 1alpha,25-dihydroxyvitamin D3. J Biol Chem. 2010;285:15599–610.PubMedCrossRefGoogle Scholar
  145. 145.
    Miller GJ, Stapleton GE, Hedlund TE, Moffat KA. Vitamin D receptor expression, 24-hydroxylase activity, and inhibition of growth by 1alpha,25-dihydroxyvitamin D3 in seven human prostatic carcinoma cell lines. Clin Cancer Res. 1995;1:997–1003.PubMedGoogle Scholar
  146. 146.
    Mimori K, Tanaka Y, Yoshinaga K, Masuda T, Yamashita K, Okamoto M, Inoue H, Mori M. Clinical significance of the overexpression of the candidate oncogene CYP24 in esophageal cancer. Ann Oncol. 2004;15:236–41.PubMedCrossRefGoogle Scholar
  147. 147.
    Mitschele T, Diesel B, Friedrich M, Meineke V, Maas RM, Gartner BC, Kamradt J, Meese E, Tilgen W, Reichrath J. Analysis of the vitamin D system in basal cell carcinomas (BCCs). Lab Invest. 2004;84:693–702.PubMedCrossRefGoogle Scholar
  148. 148.
    Murayama A, Kim MS, Yanagisawa J, Takeyama K, Kato S. Transrepression by a liganded nuclear receptor via a bHLH activator through co-regulator switching. EMBO J. 2004;23:1598–608.PubMedCrossRefGoogle Scholar
  149. 149.
    Murayama E, Miyamoto K, Kubodera N, Mori T, Matsunaga I. Synthetic studies of vitamin D3 analogues. VIII. Synthesis of 22-oxavitamin D3 analogues. Chem Pharm Bull(Tokyo). 1986;34:4410–3.CrossRefGoogle Scholar
  150. 150.
    Naja RP, Dardenne O, Arabian A, St Arnaud R. Chondrocyte-specific modulation of Cyp27b1 expression supports a role for local synthesis of 1,25-dihydroxyvitamin D3 in growth plate development. Endocrinology. 2009;150:4024–32.PubMedCrossRefGoogle Scholar
  151. 151.
    National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1-266.Google Scholar
  152. 152.
    National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42:S1-201.Google Scholar
  153. 153.
    Nemere I, Farach-Carson MC, Rohe B, Sterling TM, Norman AW, Boyan BD, Safford SE. Ribozyme knockdown functionally links a 1,25(OH)2D3 membrane binding protein (1,25D3-MARRS) and phosphate uptake in intestinal cells. Proc Natl Acad Sci USA. 2004;101:7392–7.PubMedCrossRefGoogle Scholar
  154. 154.
    Nishii Y, Sato K, Kobayashi T. The development of vitamin D3 analogues for the treatment of osteoporosis. Osteoporos Int. 1993;3 Suppl 1:190–3.PubMedCrossRefGoogle Scholar
  155. 155.
    Noda M, Vogel RL, Craig AM, Prahl J, DeLuca HF, Denhardt DT. Identification of a DNA sequence responsible for binding of the 1,25-dihydroxyvitamin D3 receptor and 1,25-dihydroxyvitamin D3 enhancement of mouse secreted phosphoprotein 1 (Spp-1 or osteopontin) gene expression. Proc Natl Acad Sci USA. 1990;87:9995–9.PubMedCrossRefGoogle Scholar
  156. 156.
    Ohyama Y, Ozono K, Uchida M, Shinki T, Kato S, Suda T, Yamamoto O, Noshiro M, Kato Y. Identification of a vitamin D-responsive element in the 5′-flanking region of the rat 25-hydroxyvitamin D3 24-hydroxylase gene. J Biol Chem. 1994;269:10545–50.PubMedGoogle Scholar
  157. 157.
    Okuda KI, Usui E, Ohyama Y. Recent progress in enzymology and molecular biology of enzymes involved in vitamin D metabolism. J Lipid Res. 1995;36:1641–52.PubMedGoogle Scholar
  158. 158.
    Omdahl JL, Bobrovnikova EA, Choe S, Dwivedi PP, May BK. Overview of regulatory cytochrome P450 enzymes of the vitamin D pathway. Steroids. 2001;66:381–9.PubMedCrossRefGoogle Scholar
  159. 159.
    Omdahl JL, Bobrovnikova EV, Annalora A, Chen P, Serda R. Expression, structure-function, and molecular modeling of vitamin D P450s. J Cell Biochem. 2003;88:356–62.PubMedCrossRefGoogle Scholar
  160. 160.
    Omdahl JL, Morris HA, May BK. Hydroxylase enzymes of the vitamin D pathway: expression, function, and regulation. Annu Rev Nutr. 2002;22:139–66.PubMedCrossRefGoogle Scholar
  161. 161.
    Onate S, Tsai S, Tsai M, O’Malley B. Sequence and characterization of a coactivator for the steroid ­hormone receptor superfamily. Science. 1995;270:1354–7.PubMedCrossRefGoogle Scholar
  162. 162.
    Orimo H, Shiraki M, Hayashi T, Nakamura T. Reduced occurrence of vertebral crush fractures in senile osteoporosis treated with 1 alpha (OH)-vitamin D3. Bone Miner. 1987;3:47–52.PubMedGoogle Scholar
  163. 163.
    Orwoll E, Nielson CM, Marshall LM, Lambert L, Holton KF, Hoffman AR, Barrett-Connor E, Shikany JM, Dam T, Cauley JA. Vitamin D deficiency in older men. J Clin Endocrinol Metab. 2009;94:1214–22.PubMedCrossRefGoogle Scholar
  164. 164.
    Ozono K, Liao J, Kerner SA, Scott RA, Pike JW. The vitamin D-responsive element in the human osteocalcin gene: association with a nuclear proto-oncogene enhancer. J Biol Chem. 1990;265:21881–8.PubMedGoogle Scholar
  165. 165.
    Paaren HE, Hamer DE, Schnoes HK, DeLuca HF. Direct C-1 hydroxylation of vitamin D compounds: convenient preparation of 1alpha-hydroxyvitamin D3, 1alpha, 25-dihydroxyvitamin D3, and 1alpha-hydroxyvitamin D2. Proc Natl Acad Sci USA. 1978;75:2080–1.PubMedCrossRefGoogle Scholar
  166. 166.
    Panda DK, Al Kawas S, Seldin MF, Hendy GN, Goltzman D. 25-hydroxyvitamin D 1alpha-hydroxylase: structure of the mouse gene, chromosomal assignment, and developmental expression. J Bone Miner Res. 2001;16:46–56.PubMedCrossRefGoogle Scholar
  167. 167.
    Panda DK, Miao D, Tremblay ML, Sirois J, Farookhi R, Hendy GN, Goltzman D. Targeted ablation of the 25-hydroxyvitamin D 1alpha -hydroxylase enzyme: evidence for skeletal, reproductive, and immune dysfunction. Proc Natl Acad Sci USA. 2001;98:7498–503.PubMedCrossRefGoogle Scholar
  168. 168.
    Parise RA, Egorin MJ, Kanterewicz B, Taimi M, Petkovich M, Lew AM, Chuang SS, Nichols M, El-Hefnawy T, Hershberger PA. CYP24, the enzyme that catabolizes the antiproliferative agent vitamin D, is increased in lung cancer. Int J Cancer. 2006;119:1819–28.PubMedCrossRefGoogle Scholar
  169. 169.
    Patel UD, Young EW, Ojo AO, Hayward RA. CKD progression and mortality among older patients with diabetes. Am J Kidney Dis. 2005;46:406–14.PubMedCrossRefGoogle Scholar
  170. 170.
    Peng J, Chen X, Berger U, Vassilev P, Tsukaguchi H, Brown E, Hediger M. Molecular cloning and characterization of a channel-like transporter mediating intestinal calcium absorption. J Biol Chem. 1999;274:22739–46.PubMedCrossRefGoogle Scholar
  171. 171.
    Portale AA, Miller WL. Human 25-hydroxyvitamin D-1alpha-hydroxylase: cloning, mutations, and gene expression. Pediatr Nephrol. 2000;14:620–5.PubMedCrossRefGoogle Scholar
  172. 172.
    Posner GH, Helvig C, Cuerrier D, Collop D, Kharebov A, Ryder K, Epps T, Petkovich M. Vitamin D analogues targeting CYP24 in chronic kidney disease. J Steroid Biochem Mol Biol. 2010;121(1–2):13–9.PubMedCrossRefGoogle Scholar
  173. 173.
    Posner GH, Wang Q, Han G, Lee JK, Crawford K, Zand S, Brem H, Peleg S, Dolan P, Kensler TW. Conceptually new sulfone analogues of the hormone 1alpha, 25-dihydroxyvitamin D(3): synthesis and preliminary biological evaluation. J Med Chem. 1999;42:3425–35.PubMedCrossRefGoogle Scholar
  174. 174.
    Prosser DE, Kaufmann M, O’Leary B, Byford V, Jones G. Single A326G mutation converts human CYP24A1 from 25-OH-D3–24-hydroxylase into -23-hydroxylase, generating 1alpha,25-(OH)2D3–26,23-lactone. Proc Natl Acad Sci USA. 2007;104:12673–8.PubMedCrossRefGoogle Scholar
  175. 175.
    Puzas JE, Turner RT, Howard GA, Brand JS, Baylink DJ. Synthesis of 1,25-dihydroxycholecalciferol and 24,25- dihydroxycholecalciferol by calvarial cells. Characterization of the enzyme systems. Biochem J. 1987;245:333–8.PubMedGoogle Scholar
  176. 176.
    Rachez C, Lemon B, Suldan Z, Bromleigh B,Gamble M, Naar N, Erdjument-Bromage H, Tempst P, Freedman LP. Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature. 1999;398:824–8.PubMedCrossRefGoogle Scholar
  177. 177.
    Rachez C, Suldan Z, Ward J, Chang CP, Burakov D, Erdjument-Bromage H, Tempst P, Freedman LP. A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system. Genes Dev. 1998;12:1787–800.PubMedCrossRefGoogle Scholar
  178. 178.
    Raggi P, Boulay A, Chasan-Taber S, Amin N, Dillon M, Burke SK, Chertow GM. Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease? J Am Coll Cardiol. 2002;39:695–701.PubMedCrossRefGoogle Scholar
  179. 179.
    Raggi P, Kleerekoper M. Contribution of bone and mineral abnormalities to cardiovascular disease in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2008;3:836–43.PubMedCrossRefGoogle Scholar
  180. 180.
    Rahmaniyan M, Patrick K, Bell NH. Characterization of recombinant CYP2C11: a vitamin D 25-hydroxylase and 24-hydroxylase. Am J Physiol Endocrinol Metab. 2005;288:E753–60.PubMedCrossRefGoogle Scholar
  181. 181.
    Rao A, Woodruff RD, Wade WN, Kute TE, Cramer SD. Genistein and vitamin D synergistically inhibit human prostatic epithelial cell growth. J Nutr. 2002;132:3191–4.PubMedGoogle Scholar
  182. 182.
    Reade TM, Scriver CR, Glorieux FH, Nogrady B, Delvin E, Poirier R, Holick F, DeLuca HF. Response to crystalline 1alpha-hydroxyvitamin D3 in vitamin D dependency. Pediatr Res. 1975;9:593–9.PubMedCrossRefGoogle Scholar
  183. 183.
    Reichel H, Bishop JE, Koeffler HP, Norman AW. Evidence for 1,25-dihydroxyvitamin D3 production by cultured porcine alveolar macrophages. Mol Cell Endocrinol. 1991;75:163–7.PubMedCrossRefGoogle Scholar
  184. 184.
    Reichrath J, Rafi L, Rech M, Mitschele T, Meineke V, Gartner BC, Tilgen W, Holick MF. Analysis of the vitamin D system in cutaneous squamous cell carcinomas. J Cutan Pathol. 2004;31:224–31.PubMedCrossRefGoogle Scholar
  185. 185.
    Reinhardt TA, Horst RL. Self-induction of 1,25-dihydroxyvitamin D3 metabolism limits receptor occupancy and target tissue responsiveness. J Biol Chem. 1989;264:15917–21.PubMedGoogle Scholar
  186. 186.
    Roff A, Wilson RT. A novel SNP in a vitamin D response element of the CYP24A1 promoter reduces protein ­binding, transactivation, and gene expression. J Steroid Biochem Mol Biol. 2008;112:47–54.PubMedCrossRefGoogle Scholar
  187. 187.
    Rosen H, Reshef A, Maeda N, Lippoldt A, Shpizen S, Triger L, Eggertsen G, Bjorkhem I, Leitersdorf E. Markedly reduced bile acid synthesis but maintained levels of cholesterol and vitamin D metabolites in mice with disrupted sterol 27-hydroxylase gene. J Biol Chem. 1998;273:14805–12.PubMedCrossRefGoogle Scholar
  188. 188.
    Saini SP, Sonoda J, Xu L, Toma D, Uppal H, Mu Y, Ren S, Moore DD, Evans RM, Xie W. A novel constitutive androstane receptor-mediated and CYP3A-independent pathway of bile acid detoxification. Mol Pharmacol. 2004;65:292–300.PubMedCrossRefGoogle Scholar
  189. 189.
    Saito H, Kusano K, Kinosaki M, Ito H, Hirata M, Segawa H, Miyamoto K, Fukushima N. Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production. J Biol Chem. 2003;278:2206–11.PubMedCrossRefGoogle Scholar
  190. 190.
    Sakai Y, Demay MB. Evaluation of keratinocyte proliferation and differentiation in vitamin D receptor knockout mice. Endocrinology. 2000;141:2043–9.PubMedCrossRefGoogle Scholar
  191. 191.
    Sakai Y, Kishimoto J, Demay MB. Metabolic and cellular analysis of alopecia in vitamin D receptor knockout mice. J Clin Invest. 2001;107:961–6.PubMedCrossRefGoogle Scholar
  192. 192.
    Sakaki T, Sawada N, Komai K, Shiozawa S, Yamada S, Yamamoto K, Ohyama Y, Inouye K. Dual metabolic pathway of 25-hydroxyvitamin D3 catalyzed by human CYP24. Eur J Biochem FEBS. 2000;267:6158–65.CrossRefGoogle Scholar
  193. 193.
    Sakati N, Woodhouse NJ, Niles N, Harfi H, de Grange DA, Marx S. Hereditary resistance to 1,25-dihydroxyvitamin D: clinical and radiological improvement during high-dose oral calcium therapy. Horm Res. 1986;24:280–7.PubMedCrossRefGoogle Scholar
  194. 194.
    Salen G, Shefer S, Cheng FW, Dayal B, Batta AK, Tint GS. Cholic acid biosynthesis: the enzymatic defect in cerebrotendinous xanthomatosis. J Clin Invest. 1979;63:38–44.PubMedCrossRefGoogle Scholar
  195. 195.
    Salusky IB. Are new vitamin D analogues in renal bone disease superior to calcitriol? Pediatr Nephrol. 2005;20:393–8.PubMedCrossRefGoogle Scholar
  196. 196.
    Sanchez-Martinez R, Zambrano A, Castillo AI, Aranda A. Vitamin D-dependent recruitment of corepressors to vitamin D/retinoid X receptor heterodimers. Mol Cell Biol. 2008;28:3817–29.PubMedCrossRefGoogle Scholar
  197. 197.
    Schwartz Z, Brooks B, Swain L, Del Toro F, Norman A, Boyan B. Production of 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 by growth zone and resting zone chondrocytes is dependent on cell maturation and is regulated by hormones and growth factors. Endocrinology. 1992;130:2495–504.PubMedCrossRefGoogle Scholar
  198. 198.
    Schwartz Z, Graham EJ, Wang L, Lossdorfer S, Gay I, Johnson-Pais TL, Carnes DL, Sylvia VL, Boyan BD. Phospholipase A2 activating protein (PLAA) is required for 1alpha,25(OH)2D3 signaling in growth plate chondrocytes. J Cell Physiol. 2005;203:54–70.PubMedCrossRefGoogle Scholar
  199. 199.
    Schwartz Z, Shaked D, Hardin RR, Gruwell S, Dean DD, Sylvia VL, Boyan BD. 1alpha,25(OH)2D3 causes a rapid increase in phosphatidylinositol-specific PLC-beta activity via phospholipase A2-dependent production of lysophospholipid. Steroids. 2003;68:423–37.PubMedCrossRefGoogle Scholar
  200. 200.
    Schwartz Z, Sylvia VL, Luna MH, DeVeau P, Whetstone R, Dean DD, Boyan BD. The effect of 24R,25-(OH)(2)D(3) on protein kinase C activity in chondrocytes is mediated by phospholipase D whereas the effect of 1alpha,25-(OH)(2)D(3) is mediated by phospholipase C. Steroids. 2001;66:683–94.PubMedCrossRefGoogle Scholar
  201. 201.
    Scriver CR. Vitamin D dependency. Pediatrics. 1970;45:361–3.PubMedGoogle Scholar
  202. 202.
    Scriver CR, Reade TM, DeLuca HF, Hamstra AJ. Serum 1,25-dihydroxyvitamin D levels in normal subjects and in patients with hereditary rickets or bone disease. N Engl J Med. 1978;299:976–9.PubMedCrossRefGoogle Scholar
  203. 203.
    Shaul PW, Anderson RG. Role of plasmalemmal caveolae in signal transduction. Am J Physiol. 1998;275:L843–51.PubMedGoogle Scholar
  204. 204.
    Shinki T, Shimada H, Wakino S, Anazawa H, Hayashi M, Saruta T, DeLuca HF, Suda T. Cloning and expression of rat 25-hydroxyvitamin D3–1alpha-hydroxylase cDNA. Proc Natl Acad Sci USA. 1997;94:12920–5.PubMedCrossRefGoogle Scholar
  205. 205.
    Slatopolsky E, Gonzalez E, Martin K. Pathogenesis and treatment of renal osteodystrophy. Blood Purif. 2003;21:318–26.PubMedCrossRefGoogle Scholar
  206. 206.
    Smith SJ, Rucka AK, Berry JL, Davies M, Mylchreest S, Paterson CR, Heath DA, Tassabehji M, Read AP, Mee AP, Mawer EB. Novel mutations in the 1alpha-hydroxylase (P450c1) gene in three families with pseudovitamin D-deficiency rickets resulting in loss of functional enzyme activity in blood-derived macrophages. J Bone Miner Res. 1999;14:730–9.PubMedCrossRefGoogle Scholar
  207. 207.
    Sonoda G, Palazzo J, du Manoir S, Godwin AK, Feder M, Yakushiji M, Testa JR. Comparative genomic hybridization detects frequent overrepresentation of chromosomal material from 3q26, 8q24, and 20q13 in human ovarian carcinomas. Genes Chromosomes Cancer. 1997;20:320–8.PubMedCrossRefGoogle Scholar
  208. 208.
    Spencer T, Jenster G, Burcin M, Allis C, Zhou J, Mizzen C, McKenna NJ, Onate S, Tsai S, Tsai M, O’Malley B. Steroid receptor coactivator-1 is a histone acetyltransferase. Nature. 1997;389:194–8.PubMedCrossRefGoogle Scholar
  209. 209.
    St-Arnaud R, Arabian A, Travers R, Barletta F, Raval-Pandya M, Chapin K, Depovere J, Mathieu C, Christakos S, Demay MB, Glorieux FH. Deficient mineralization of intramembranous bone in vitamin D-24-hydroxylase-ablated mice is due to elevated 1,25-dihydroxyvitamin D and not to the absence of 24,25-dihydroxyvitamin D. Endocrinology. 2000;141:2658–66.PubMedCrossRefGoogle Scholar
  210. 210.
    St-Arnaud R, Messerlian S, Moir JM, Omdahl JL, Glorieux FH. The 25-hydroxyvitamin D 1-alpha-hydroxylase gene maps to the pseudovitamin D-deficiency rickets (PDDR) disease locus. J Bone Miner Res. 1997;12:1552–9.PubMedCrossRefGoogle Scholar
  211. 211.
    Steddon SJ, Fan SL, Cunningham J. New prospects for the management of renal bone disease. Nephron Clin Pract. 2005;99:c1–7.PubMedCrossRefGoogle Scholar
  212. 212.
    Strushkevich N, Usanov SA, Plotnikov AN, Jones G, Park HW. Structural analysis of CYP2R1 in complex with vitamin D3. J Mol Biol. 2008;380:95–106.PubMedCrossRefGoogle Scholar
  213. 213.
    Swami S, Krishnan AV, Moreno J, Bhattacharyya RB, Peehl DM, Feldman D. Calcitriol and genistein actions to inhibit the prostaglandin pathway: potential combination therapy to treat prostate cancer. J Nutr. 2007;137:205S–10.PubMedGoogle Scholar
  214. 214.
    Takamoto M, Tsuji K, Yamashita T, Sasaki H, Yano T, Taketani Y, Komori T, Nifuji A, Noda M. Hedgehog signaling enhances core-binding factor a1 and receptor activator of nuclear factor-kappaB ligand (RANKL) gene expression in chondrocytes. J Endocrinol. 2003;177:413–21.PubMedCrossRefGoogle Scholar
  215. 215.
    Takeda E, Kuroda Y, Saijo T, Naito E, Kobashi H, Yokota I, Miyao M. 1 alpha-hydroxyvitamin D3 treatment of three patients with 1,25-dihydroxyvitamin D-receptor-defect rickets and alopecia. Pediatrics. 1987;80:97–101.PubMedGoogle Scholar
  216. 216.
    Takeshita A, Yen P, Misiti S, Cardona G, Liu Y, Chin W. Molecular cloning and properties of a full-length putative thyroid hormone receptor coactivator. Endocrinology. 1996;137:3594–7.PubMedCrossRefGoogle Scholar
  217. 217.
    Takeyama K, Kitanaka S, Sato T, Kobori M, Yanagisawa J, Kato S. 25-Hydroxyvitamin D3 1alpha-hydroxylase and vitamin D synthesis. Science. 1997;277:1827–30.PubMedCrossRefGoogle Scholar
  218. 218.
    Tanner MM, Grenman S, Koul A, Johannsson O, Meltzer P, Pejovic T, Borg A, Isola JJ. Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer. Clin Cancer Res. 2000;6:1833–9.PubMedGoogle Scholar
  219. 219.
    Toell A, Gonzalez MM, Ruf D, Steinmeyer A, Ishizuka S, Carlberg C. Different molecular mechanisms of vitamin D(3) receptor antagonists. Mol Pharmacol. 2001;59:1478–85.PubMedGoogle Scholar
  220. 220.
    Tomon M, Tenenhouse HS, Jones G. Expression of 25-hydroxyvitamin D3–24-hydroxylase activity in Caco-2 cells. An in vitro model of intestinal vitamin D catabolism. Endocrinology. 1990;126:2868–75.PubMedCrossRefGoogle Scholar
  221. 221.
    Tsuchiya Y, Matsuo N, Cho H, Kumagai M, Yasaka A, Suda T, Orimo H, Shiraki M. An unusual form of vitamin D-dependent rickets in a child: alopecia and marked end-organ hyposensitivity to biologically active vitamin D. J Clin Endocrinol Metab. 1980;51:685–90.PubMedCrossRefGoogle Scholar
  222. 222.
    Umesono K, Murakami KK, Thompson CC, Evans RM. Direct repeats as selective response elements for the thyroid hormone, retinoic acid and vitamin D3 receptors. Cell. 1991;65:1255–66.PubMedCrossRefGoogle Scholar
  223. 223.
    Uppal H, Saini SP, Moschetta A, Mu Y, Zhou J, Gong H, Zhai Y, Ren S, Michalopoulos GK, Mangelsdorf DJ, Xie W. Activation of LXRs prevents bile acid toxicity and cholestasis in female mice. Hepatology. 2007;45:422–32.PubMedCrossRefGoogle Scholar
  224. 224.
    van Deurs B, Roepstorff K, Hommelgaard AM, Sandvig K. Caveolae: anchored, multifunctional platforms in the lipid ocean. Trends Cell Biol. 2003;13:92–100.PubMedCrossRefGoogle Scholar
  225. 225.
    Wagner D, Hanwell HE, Vieth R. An evaluation of automated methods for measurement of serum 25-hydroxyvitamin D. Clin Biochem. 2009;42:1549–56.PubMedCrossRefGoogle Scholar
  226. 226.
    Wang JT, Lin CJ, Burridge SM, Fu GK, Labuda M, Portale AA, Miller WL. Genetics of vitamin D 1alpha-hydroxylase deficiency in 17 families. Am J Hum Genet. 1998;63:1694–702.PubMedCrossRefGoogle Scholar
  227. 227.
    Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-Mendoza L, Lin R, Hanrahan JW, Mader S, White JH. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004;173:2909–12.PubMedGoogle Scholar
  228. 228.
    Wang X, Zhang MY, Miller WL, Portale AA. Novel gene mutations in patients with 1alpha-hydroxylase deficiency that confer partial enzyme activity in vitro. J Clin Endocrinol Metab. 2002;87:2424–30.PubMedCrossRefGoogle Scholar
  229. 229.
    Wasserman RH, Fullmer CS. Calcium transport proteins, calcium absorption, and vitamin D. Ann Rev Physiol. 1983;45:375–90.CrossRefGoogle Scholar
  230. 230.
    Weber G, Heilborn JD, Chamorro Jimenez CI, Hammarsjo A, Torma H, Stahle M. Vitamin D induces the antimicrobial protein hCAP18 in human skin. J Invest Dermatol. 2005;124:1080–2.PubMedCrossRefGoogle Scholar
  231. 231.
    Weisman Y, Bab I, Gazit D, Spirer Z, Jaffe M, Hochberg Z. Long-term intracaval calcium infusion therapy in end-organ resistance to 1,25-dihydroxyvitamin D. Am J Med. 1987;83:984–90.PubMedCrossRefGoogle Scholar
  232. 232.
    Weiss MM, Snijders AM, Kuipers EJ, Ylstra B, Pinkel D, Meuwissen SG, van Diest PJ, Albertson DG, Meijer GA. Determination of amplicon boundaries at 20q13.2 in tissue samples of human gastric adenocarcinomas by high-resolution microarray comparative genomic hybridization. J Pathol. 2003;200:320–6.PubMedCrossRefGoogle Scholar
  233. 233.
    Werner M, Mattis A, Aubele M, Cummings M, Zitzelsberger H, Hutzler P, Hofler H. 20q13.2 amplification in intraductal hyperplasia adjacent to in situ and invasive ductal carcinoma of the breast. Virchows Arch. 1999;435:469–72.PubMedCrossRefGoogle Scholar
  234. 234.
    Whitfield GK, Selznick SH, Haussler CA, Hsieh JC, Galligan MA, Jurutka PW, Thompson PD, Lee SM, Zerwekh JE, Haussler MR. Vitamin D receptors from patients with resistance to 1,25-dihydroxyvitamin D3: point mutations confer reduced transactivation in response to ligand and impaired interaction with the retinoid X receptor heterodimeric partner. Mol Endocrinol. 1996;10:1617–31.PubMedCrossRefGoogle Scholar
  235. 235.
    Wietzke JA, Welsh J. Phytoestrogen regulation of a Vitamin D3 receptor promoter and 1,25-dihydroxyvitamin D3 actions in human breast cancer cells. J Steroid Biochem Mol Biol. 2003;84:149–57.PubMedCrossRefGoogle Scholar
  236. 236.
    Wolter H, Gottfried HW, Mattfeldt T. Genetic changes in stage pT2N0 prostate cancer studied by comparative genomic hybridization. BJU Int. 2002;89:310–6.PubMedCrossRefGoogle Scholar
  237. 237.
    Yamagata M, Kimoto A, Michigami T, Nakayama M, Ozono K. Hydroxylases involved in vitamin D metabolism are differentially expressed in murine embryonic kidney: application of whole mount in situ hybridization. Endocrinology. 2001;142:3223–30.PubMedCrossRefGoogle Scholar
  238. 238.
    Yee SW, Campbell MJ, Simons C. Inhibition of vitamin D3 metabolism enhances VDR signalling in androgen-independent prostate cancer cells. J Steroid Biochem Mol Biol. 2006;98:228–35.PubMedCrossRefGoogle Scholar
  239. 239.
    Yoshida T, Monkawa T, Tenenhouse HS, Goodyer P, Shinki T, Suda T, Wakino S, Hayashi M, Saruta T. Two novel 1alpha-hydroxylase mutations in French-Canadians with vitamin D dependency rickets type I. Kidney Int. 1998;54:1437–43.PubMedCrossRefGoogle Scholar
  240. 240.
    Zasloff M. Antimicrobial peptides of multicellular organisms. Nature. 2002;415:389–95.PubMedCrossRefGoogle Scholar
  241. 241.
    Zehnder D, Quinkler M, Eardley KS, Bland R, Lepenies J, Hughes SV, Raymond NT, Howie AJ, Cockwell P, Stewart PM, Hewison M. Reduction of the vitamin D hormonal system in kidney disease is associated with increased renal inflammation. Kidney Int. 2008;74:1343–53.PubMedCrossRefGoogle Scholar
  242. 242.
    Zerwekh JE, Glass K, Jowsey J, Pak CY. An unique form of osteomalacia associated with end organ refractoriness to 1,25-dihydroxyvitamin D and apparent defective synthesis of 25-hydroxyvitamin D. J Clin Endocrinol Metab. 1979;49:171–5.PubMedCrossRefGoogle Scholar
  243. 243.
    Zinser GM, McEleney K, Welsh J. Characterization of mammary tumor cell lines from wild type and vitamin D3 receptor knockout mice. Mol Cell Endocrinol. 2003;200:67–80.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2012

Authors and Affiliations

  • René St-Arnaud
    • 1
    • 2
  • Marie B. Demay
    • 3
  1. 1.Departments of Medicine, Surgery, and Human GeneticsMcGill UniversityMontrealCanada
  2. 2.Genetics UnitShriners Hospital for ChildrenMontrealCanada
  3. 3.Endocrine Unit, Department of MedicineMassachusetts General Hospital, Harvard Medical SchoolBostonUSA

Personalised recommendations