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Reshaping the way we view vitamin D signalling and the role of vitamin D in health

Published online by Cambridge University Press:  14 December 2007

James C. Fleet ,
Jie Hong  and
Zhentao Zhang
James C. Fleet*
Affiliation:
Department of Foods and Nutrition and The Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907-2059, USA
Jie Hong
Affiliation:
Department of Foods and Nutrition and The Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907-2059, USA
Zhentao Zhang
Affiliation:
Department of Foods and Nutrition and The Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907-2059, USA
*
*Corresponding author: Dr James C. Fleet, fax +1 765 494 0906, email [email protected]
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Abstract

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Although the biological requirement for vitamin D can be met by epidermal exposure to UV light, there are a number of conditions where this production does not occur or is not sufficient to meet biological needs. When this happens, vitamin D must be consumed and is a nutrient. However, two distinct observations have caused researchers to rethink certain dogma in vitamin D biology. First, it appears that in addition to the hormonally active form of 1,25 dihydroxyvitamin D (1,25(OH)2D), circulating levels of 25 hydroxyvitamin D have a critical importance for optimal human health. This and other data suggest that extra-renal production of 1,25(OH)2D contributes to Ca homeostasis and cancer prevention. Second, in addition to its role in the transcriptional activation of genes through the vitamin D receptor there is now compelling evidence that 1,25(OH)2D has a second molecular mode of action; the rapid activation of second-messenger and kinase pathways. The purpose of this second mode of action is only now being explored. The present review will discuss how these two areas are reshaping our understanding of vitamin D metabolism and action.

Keywords

Vitamin DCalcium homeostasisCancer preventionCell signalling pathways
Type
research-article
Information
Nutrition Research Reviews , Volume 17 , Issue 2 , December 2004 , pp. 241 - 248
Copyright
Copyright © The Authors 2004

References

Ahonen, MH, Tenkanen, L, Teppo, L, Hakama, M & Tuohimaa, P (2000) Prostate cancer risk and prediagnostic serum 25-hydroxy-vitamin D levels (Finland). Cancer Causes Control 11, 847–852.CrossRefGoogle Scholar
Armbrecht, HJ, Boltz, MA, Hodam, TL & Kumar, VB (2001) Differential responsiveness of intestinal epithelial cells to 1,25-dihydroxyvitamin D3 – role of protein kinase C. Journal of Endocrinology 169, 145–151.CrossRefGoogle ScholarPubMed
Baran, DT, Sorensen, AM, Shalhoub, V, Owen, T, Stein, G & Lian, J (1992) The rapid nongenomic actions of 1 alpha,25-dihydroxy- vitamin D3 modulate the hormone-induced increments in osteocalcin gene transcription in osteoblast-like cells. Journal of Cellular Biochemistry 50, 124–129.CrossRefGoogle Scholar
Barger-Lux, MJ, Heaney, RP, Lanspa, SJ, Healy, JC & DeLuca, HF (1995) An investigation of sources of variation in calcium absorption efficiency. Journal of Clinical Endocrinology and Metabolism 80, 406–411.Google ScholarPubMed
Barletta, F, Freedman, LP & Christakos, S (1995) Enhancement of VDR-mediated transcription by phosphorylation: correlation with increased interaction between the VDR and DRIP205, a subunit of the VDR-interacting protein coactivator complex. Molecular Endocrinology 16, 301–314.CrossRefGoogle Scholar
Bettoun, DJ, Burris, TP, Houck, KA, Buck, DW II, Stayrook, KR, Khalifa, B, Lu, J, Chin, WW & Nagpal, S (2003) Retinoid X receptor is a nonsilent major contributor to vitamin D receptor-mediated transcriptional activation. Molecular Endocrinology 17, 2320–2328.CrossRefGoogle ScholarPubMed
Boyan, BD, Dean, DD, Sylvia, VL & Schwartz, Z (1994) Nongenomic regulation of extracellular matrix events by vitamin D metabolites. Journal of Cellular Biochemistry 56, 331–339.CrossRefGoogle ScholarPubMed
Boyan, BD, Dean, DD, Sylvia, VL & Schwartz, Z (2003) Steroid hormone action in musculoskeletal cells involves membrane receptor and nuclear receptor mechanisms. Connective Tissue Research 44, Suppl. 1, 130–135.CrossRefGoogle ScholarPubMed
Boyan, BD, Sylvia, VL, Dean, DD, Pedrozo, H, Del Toro, F, Nemere, I, Posner, GH & Schwartz, Z (1999) 1,25-(OH)2D3 modulates growth plate chondrocytes via membrane receptor-mediated protein kinase C by a mechanism that involves changes in phospholipid metabolism and the action of arachidonic acid and PGE2. Steroids 64, 129–136.Google ScholarPubMed
Bronner, F, Pansu, D & Stein, WD (1996) An analysis of intestinal calcium transport across the rat intestine. American Journal of Physiology 250, G561–G569.Google Scholar
Brumbaugh, PF & Haussler, MR (1973) 1Alpha, 25-dihydroxyvitamin D3 receptor: competitive binding of vitamin D analogs. Life Sciences 13, 1737–1746.CrossRefGoogle ScholarPubMed
Buitrago, C, Boland, R & de Boland, AR (2001 a) The tyrosine kinase c-Src is required for 1,25(OH)2-vitamin D3 signalling to the nucleus in muscle cells. Biochimica et Biophysica Acta 1541, 179–187.CrossRefGoogle Scholar
Buitrago, C, Vazquez, G, de Boland, AR & Boland, R (2001 b) The vitamin D receptor mediates rapid changes in muscle protein tyrosine phosphorylation induced by 1,25(OH)(2)D(3). Biochemical and Biophysical Research Communications 289, 1150–1156.CrossRefGoogle Scholar
Buitrago, C, Vazquez, G, de Boland, AR & Boland, RL (2000) Activation of Src kinase in skeletal muscle cells by 1, 1,25-(OH(2))-vitamin D(3) correlates with tyrosine phosphorylation of the vitamin D receptor (VDR) and VDR-Src interaction. Journal of Cellular Biochemistry 79, 274–281.3.0.CO;2-R>CrossRefGoogle Scholar
Chapuy, MC, Preziosi, P, Maamer, M, Arnaud, S, Galan, P, Hercberg, S & Meunier, PJ (1997) Prevalence of vitamin D insufficiency in an adult normal population. Osteoporosis International 7, 439–443.CrossRefGoogle Scholar
Chen, H, Lin, RJ, Xie, W, Wilpitz, D & Evans, RM (1999) Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase. Cell 98, 675–686.CrossRefGoogle ScholarPubMed
Chiba, N, Suldan, Z, Freedman, L & Parvin, J (2000) Binding of liganded vitamin D receptor to the vitamin D receptor interacting protein coactivator complex induces interaction with RNA polymerase II holoenzyme. Journal of Biological Chemistry 275, 10719–10722.CrossRefGoogle Scholar
Dawson-Hughes, B, Harris, S, Kramich, C, Dallal, G & Rasmussen, HM (1993) Calcium retention and hormone levels in black and white women on high- and low-calcium diets. Journal of Bone and Mineral Research 8, 779–787.CrossRefGoogle ScholarPubMed
Demay, MB, Kiernan, MS, DeLuca, HF & Kronenberg, HM (1992) Sequences in the human parathyroid hormone gene that bind the 1,25-dihydroxyvitamin D3 receptor and mediate transcriptional repression in response to 1,25-dihydroxyvitamin D3. Proceedings of the National Academy of Sciences USA 89, 8097–8101.CrossRefGoogle Scholar
Desai, RK, van Wijnen, AJ, Stein, JL, Stein, GL & Lian, JB (1995) Control of 1,25-dihydroxyvitamin D3 receptor-mediated enhancement of osteoclacin gene transcription: effects of perturbing phosphorylation pathways by okadaic acid and staurosporine. Endocrinology 136, 5685–5693.CrossRefGoogle Scholar
Devine, A, Wilson, SG, Dick, IM & Prince, RL (2002) Effects of vitamin D metabolites on intestinal calcium absorption and bone turnover in elderly women. American Journal of Clinical Nutrition 75, 283–288.CrossRefGoogle ScholarPubMed
Dusso, A, Lopez-Hilker, S, Rapp, N & Slatopolsky, E (1988) Extra-renal production of calcitriol in chronic renal failure. Kidney International 34, 368–375.CrossRefGoogle ScholarPubMed
Dwivedi, PP, Hii, CS, Ferrante, A, Tan, J, Der, CJ, Omdahl, JL, Morris, HA & May, BK (2002) Role of MAP kinases in the 1,25-dihydroxyvitamin D3-induced transactivation of the rat cytochrome P450C24 (CYP24) promoter. Specific functions for ERK1/ERK2 and ERK5. Journal of Biological Chemistry 277, 29643–29653.CrossRefGoogle Scholar
Erben, RG, Soegiarto, DW, Weber, K, Zeitz, U, Lieberherr, M, Gniadecki, R, Moller, G, Adamski, J & Balling, R (2002) Deletion of deoxyribonucleic acid binding domain of the vitamin D receptor abrogates genomic and nongenomic functions of vitamin D. Molecular Endocrinology 16, 1524–1537.CrossRefGoogle ScholarPubMed
Farach-Carson, MC & Nemere, I (2003) Membrane receptors for vitamin D steroid hormones: potential new drug targets. Current Drug Targets 4, 67–76.CrossRefGoogle ScholarPubMed
Freedman, LP (1999) Increasing the complexity of coactivation in nuclear receptor signaling. Cell 97, 5–8.CrossRefGoogle ScholarPubMed
Glorieux, FH & St-Arnaud, R (1997) Vitamin D Pseudodeficiency. InVitamin D pp. 755–764. [DD Feldman,, FHGloriex and, JW Pike editors]. San Diego, CA: Academic Press.Google ScholarPubMed
Haddad, JG Jr & Rojanasathit, S (1976) Acute administration of 25-hydroxycholecalciferol in man. Journal of Clinical Endocrinology and Metabolism 42, 284–290.CrossRefGoogle ScholarPubMed
Hanchette, CL & Schwartz, GG (1992) Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation. Cancer 70, 2861–2869.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Hara, H, Yasunami, Y & Adachi, T (2002) Alteration of cellular phosphorylation state affects vitamin D receptor-mediated CYP3A4 mRNA induction in Caco-2 cells. Biochemical and Biophysical Research Communications 296, 182–188.CrossRefGoogle ScholarPubMed
Harvey, BJ, Alzamora, R, Healy, V, Renard, C & Doolan, CM (2002) Rapid responses to steroid hormones: from frog skin to human colon. A homage to Hans Ussing. Biochimica et Biophysica Acta 1566, 116–128.CrossRefGoogle Scholar
Haussler, MR, Whitfield, GK, Haussler, CA, Hsieh, JC, Thompson, PD, Selznick, SH, Dominguez, CE & Jurutka, PW (1998) The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. Journal of Bone and Mineral Research 13, 325–349.CrossRefGoogle ScholarPubMed
Heaney, RP, Barger-Lux, MJ, Dowell, MS, Chen, TC & Holick, MF (1997) Calcium absorptive effects of vitamin D and its major metabolites. Journal of Clinical Endocrinology and Metabolism 82, 4111–4116.Google ScholarPubMed
Heaney, RP, Dowell, MS, Hale, CA & Bendich, A (2003) Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. Journal of the American College of Nutrition 22, 142–146.CrossRefGoogle ScholarPubMed
Hedlund, TE, Moffatt, KA & Miller, GJ (1996 a) Stable expression of the nuclear vitamin D receptor in the human prostatic carcinoma cell line JCA-1: evidence that the antiproliferative effects of 1 alpha, 25-dihydroxyvitamin D3 are mediated exclusively through the genomic signaling pathway. Endocrinology 137, 1554–1561.CrossRefGoogle ScholarPubMed
Hedlund, TE, Moffatt, KA & Miller, GJ (1996 b) Vitamin D receptor expression is required for growth modulation by 1 alpha,25-dihydroxyvitamin D3 in the human prostatic carcinoma cell line ALVA-31. Journal of Steroid Biochemistry and Molecular Biology 58, 277–288.CrossRefGoogle ScholarPubMed
Holick, M (1997) Photobiology of vitamin D. In Vitamin D pp. 33–39 [Feldman, D, Glorieux, F and Pike, J editors]. San Diego, CA: Academic Press.Google Scholar
Holick, MF (2003) Vitamin D: A millennium perspective. Journal of Cellular Biochemistry 88, 296–307.CrossRefGoogle Scholar
Hsu, JY, Feldman, D, McNeal, JE & Peehl, DM (2001) Reduced 1alpha-hydroxylase activity in human prostate cancer cells correlates with decreased susceptibility to 25-hydroxyvitamin D3-induced growth inhibition. Cancer Research 61, 2852–2856.Google ScholarPubMed
Jongen, MJ, van der Vijgh, WJ, Lips, P & Netelenbos, JC (1984) Measurement of vitamin D metabolites in anephric subjects. Nephron 36, 230–234.CrossRefGoogle ScholarPubMed
Koyama, H, Inaba, M, Nishizawa, Y, Ohno, S & Morii, H (1994) Protein kinase C is involved in 24-hydroxylase gene expression induced by 1,25 (OH) 2 D 3 in rat intestinal epithelial cells. Journal of Cellular Biochemistry 55, 230–240.CrossRefGoogle Scholar
Lee, KC, Li, J, Cole, PA, Wong, J & Kraus, WL (2003) Transcriptional activation by thyroid hormone receptor-beta involves chromatin remodeling, histone acetylation, and synergistic stimulation by p300 and steroid receptor coactivators. Molecular Endocrinology 17, 908–922.CrossRefGoogle ScholarPubMed
MacLaughlin, JA, Anderson, RR & Holick, MF (1982) Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin. Science 216, 1001–1003.CrossRefGoogle ScholarPubMed
Mason, RS, Lissner, D, Posen, S & Norman, AW (1980) Blood concentrations of dihydroxylated vitamin D metabolites after an oral dose. British Medical Journal 280, 449–450.CrossRefGoogle ScholarPubMed
Miller, GJ, Stapleton, GE, Hedlund, TE & Moffat, KA (1995) Vitamin D receptor expression, 24-hydroxylase activity, and inhibition of growth by 1 alpha, 25-dihydroxyvitamin D3 in seven human prostatic carcinoma cell lines. Clinical Cancer Research 1, 997–1003.Google ScholarPubMed
Nemere, I & Farach-Carson, MC (1998) Membrane receptors for steroid hormones: a case for specific cell surface binding sites for vitamin D metabolites and estrogens. Biochemical and Biophysical Research Communications 248, 443–449.CrossRefGoogle ScholarPubMed
Paredes, R, Gutierrez, J, Gutierrez, S, Allison, L, Puchi, M, Imschenetzky, M, van Wijnen, A, Lian, J, Stein, G, Stein, J & Montecino, M (2002) Interaction of the 1alpha,25-dihydroxyvitamin D3 receptor at the distal promoter region of the bone-specific osteocalcin gene requires nucleosomal remodelling. Biochemical Journal 363, 667–676.CrossRefGoogle Scholar
Rachez, C, Lemon, BD, Suldan, Z, Bromleigh, V, Gamble, M, Naar, AM, Erdjument-Bromage, H, Tempst, P & Freedman, LP (1999) Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature 398, 824–828.CrossRefGoogle ScholarPubMed
Rowan, BG, Weigel, NL & O'Malley, BW (2000) Phosphorylation of steroid receptor coactivator-1. Identification of the phosphorylation sites and phosphorylation through the mitogen-activated protein kinase pathway. Journal of Biological Chemistry 275, 4475–4483.CrossRefGoogle ScholarPubMed
Schwartz, GG & Hulka, BS (1990) Is vitamin D deficiency a risk factor for prostate cancer? (hypothesis). Anticancer Research 10, 1307–1311.Google ScholarPubMed
Schwartz, Z, Brooks, B, Swain, L, Deltoro, F, Norman, A & Boyan, B (1992) 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 130, 2495–2504.CrossRefGoogle ScholarPubMed
Sitrin, MD, Bissonnette, M, Bolt, MJ, Wali, R, Khare, S, Scaglione-Sewell, B, Skarosi, S & Brasitus, TA (1999) Rapid effects of 1,25(OH)2 vitamin D3 on signal transduction systems in colonic cells. Steroids 64, 137–142.CrossRefGoogle Scholar
Song, Y, Kato, S & Fleet, JC (2003 a) Vitamin D receptor (VDR) knockout mice reveal VDR-independent regulation of intestinal calcium absorption and ECaC2 and calbindin D(9k) mRNA. Journal of Nutrition 133, 374–380.CrossRefGoogle ScholarPubMed
Song, Y, Peng, X, Porta, A, Takanaga, H, Peng, JB, Hediger, MA, Fleet, JC & Christakos, S (2003 b) Calcium transporter 1 and epithelial calcium channel messenger ribonucleic acid are differentially regulated by 1,25 dihydroxyvitamin D3 in the intestine and kidney of mice. Endocrinology 144, 3885–3894.CrossRefGoogle ScholarPubMed
St Arnaud, R, Dardenne, O, Prud'homme, J, Hacking, SA& Glorieux, FH (2003) Conventional and tissue-specific inactivation of the 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1). Journal of Cellular Biochemistry 88, 245–251.CrossRefGoogle ScholarPubMed
Thomas, MK, Lloyd-Jones, DM, Thadhani, RI, Shaw, AC, Deraska, DJ, Kitch, BT, Vamvakas, EC, Dick, IM, Prince, RL & Finkelstein, JS (1998) Hypovitaminosis D in medical inpatients. New England Journal of Medicine 338, 777–783.CrossRefGoogle ScholarPubMed
Trivedi, DP, Doll, R & Khaw, KT (2003) Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. British Medical Journal 326, 469.CrossRefGoogle ScholarPubMed
van Cromphaut, SJ, Dewerchin, M, Hoenderop, JG, Stockmans, I, Van Herck, E, Kato, S, Bindels, RJ, Collen, D, Carmeliet, P, Bouillon, R & Carmeliet, G (2001) Duodenal calcium absorption in vitamin D receptor-knockout mice: functional and molecular aspects. Proceedings of the National Academy of Sciences USA 98, 13324–13329.CrossRefGoogle ScholarPubMed
Wali, RK, Kong, J, Sitrin, MD, Bissonnette, M & Li, YC (2003) Vitamin D receptor is not required for the rapid actions of 1,25-dihydroxyvitamin D3 to increase intracellular calcium and activate protein kinase C in mouse osteoblasts. Journal of Cellular Biochemistry 88, 794–801.CrossRefGoogle Scholar
Whitlatch, LW, Young, MV, Schwartz, GG, Flanagan, JN, Burnstein, KL, Lokeshwar, BL, Rich, ES, Holick, MF & Chen, TC (2002) 25-Hydroxyvitamin D-1alpha-hydroxylase activity is diminished in human prostate cancer cells and is enhanced by gene transfer. Journal of Steroid Biochemistry and Molecular Biology 81, 135–140.CrossRefGoogle ScholarPubMed
Zehnder, D, Bland, R, Williams, MC, McNinch, RW, Howie, AJ, Stewart, PM & Hewison, M (2001) Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. Journal of Clinical Endocrinology and Metabolism 86, 888–894.Google ScholarPubMed
Zhuang, SH, Schwartz, GG, Cameron, D & Burnstein, KL (1997) Vitamin D receptor content and transcriptional activity do not fully predict antiproliferative effects of vitamin D in human prostate cancer cell lines. Molecular and Cellular Endocrinology 126, 83–90.CrossRefGoogle Scholar