Vitamin D Metabolism: Role in the Genesis of Diseases
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Resumen
Vitamin D has traditionally been associated with bone metabolism, however it exerts different functions in various tissues of the body that possess the vitamin D (VCR) receptor and they are susceptible to its effect. Decreased vitamin D has also been associated with "nonclassical" diseases such as hypertension, metabolic syndrome, insulin resistance, diabetes, development of some cancers, lung disorders, autoimmunity and infertility, among others. Maternal vitamin D deficiency has been associated in the genesis of postnatal diseases. Further, many of these pathologies are produced by molecular alterations, mainly related to metabolism and receptor polymorphisms VCR. Vitamin D is considered a hormone, can be synthesized in the skin from 7-dehydrocholesterol by ultraviolet radiation B. The metabolism is complex and involves the interaction of several factors in its incorporation and final formation of calcitriol, the active form. To produce its effect requires activation of VDR receptor on the target cell, which activates specific gene sequences with different functions, through DNA promoter sequences in identified vitamin D response elements (VDRE). Many tissues have the VDR receptor and enzymes necessary for metabolism, so the spectrum of vitamin D action is very broad in the variety of pathologies produced. This review of vitamin D focuses primarily on the molecular aspects of its metabolism and its role in the genesis of "nonclassical", diseases, product of its reduction or alteration of metabolic diseases.
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Agic, A.; Xu, H.; Altgassen, C.; Noack, F.; Wolfler, M. M.; Diedrich, K.; Friedrich, M.; Taylor, R. N. & Hornung, D. Relative expression of 1,25- dihydroxyvitamin D3 receptor, vitamin D 1 alphahydroxylase, vitamin D 24-hydroxylase, and vitamin D 25-hydroxylase in endometriosis and gynecologic cancers. Reprod. Sci., 14(5):486-97, 2007.
Anagnostis, P.; Karras, S. & Goulis, D. G. Vitamin D in human reproduction: a narrative review. Int. J. Clin. Pract., 67(3):225–35, 2013.
Autier, P. Vitamin D status as a synthetic biomarker of health status. Endocrine, 51(2):201–2, 2016.
Barrera, D.; Avila, E.; Hernández, G.; Méndez, I.; González, L.; Halhali, A.; Larrea, F.; Morales, A. & Díaz, L. Calcitriol affects hCG gene transcription in cultured human syncytiotrophoblasts. Reprod. Biol. Endocrinol., 6:3, (publicado on line), 2008.
Bea, J. W.; Jurutka, P. W.; Hibler, E. A.; Lance, P.;Martínez, M. E., Roe, D. J., Sardo Molmenti, C. L.; Thompson, P. A. & Jacobs, E. T. Concentrations of the vitamin D metabolite 1,25(OH)2D and odds of metabolic syndrome and its components. Metabolism, 64(3):447–9, 2015.
Bikle, D. Nonclassic actions of vitamin D. J. Clin. Endocrinol. Metab., 94(1):26-34, 2009.
Blomberg Jensen, M.; Jørgensen, A.; Nielsen, J. E.; Bjerrum, P. J.; Skalkam, M.; Petersen, J. H.; Egeberg, D.L., Bangsbøll, S.; Andersen, A.N.; Skakkebaek, E.; Juul, A.; Rajpert-De Meyts, E.; Dissing, S.; Leffers, H. & Jørgensen, N. Expression of the vitamin D metabolizing enzyme CYP24A1 at the annulus of human spermatozoa may serve as a novel marker of semen quality. Int. J. Androl., 35(4):499-510, 2012.
Blomberg-Jensen, M. & Dissing, S. Non-genomic effects of vitamin D in human spermatozoa. Steroids, 77(10):903-9, 2012.
de Borst, M. H.; de Boer, R. A.; Stolk, R. P.; Slaets, J. P.; Wolffenbuttel, B. H. & Navis, G. Vitamin D deficiency: universal risk factor for multifactorial diseases?. Curr. Drug Targets, 12(1):97–106, 2011.
Boucher, B. J.; John, W. G. & Noonan, K. Hypovitaminosis D is associated with insulin resistance and ß cell dysfunction. Am. J. Clin. Nutr., 80(6):1666–7, 2004.
Bover, J.; Egido, J.; Fernández-Giráldez, E.; Praga, M.; Solozábal-Campos, C.; Torregrosa, J. V. & Martínez-Castelao, A. Vitamina D, receptor de la vitamina D e importancia de su activación en el paciente con enfermedad renal crónica. Nefrologia, 35(1):28-41, 2015.
Carlberg, C. & Campbell, M. J. Vitamin D receptor signaling mechanisms: integrated actions of a well-defined transcription factor. Steroids, 78(2):127–36, 2013.
Cauley, J. A.; Robbins, J.; Chen, Z.; Cummings, S. R.; Jackson, R. D.; LaCroix, A. Z.; LeBof, M.; Lewis, C. E.; McGowan, J.; Neuner, J.; Pettinger, M.; Stefanick, M. L.; Wactawski-Wende J. & Watts N. B.; Women’s Health Initiative Investigators. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women’s Health Initiative randomized trial. JAMA, 290(13):1729-38, 2003.
Chatterjee, M. Vitamin D and genomic stability. Mutat. Res., 475(1-2):69–88, 2001.
Chen, L.; Wilson, R.; Bennett, E. & Zosky, G. R. Identification of vitamin D sensitive pathways during lung development. Respir. Res., 17:47, 2016.
Cheng, J. B.; Levine, M. A.; Bell, N. H.; Mangelsdorf, D. J. & Russell, D. W. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25- hydroxylase. Proc. Natl. Acad. Sci. USA, 101(20):7711-15, 2004.
Cho, S.; Choi, Y. S.; Yim, S. Y.; Yang, H. I., Jeon, Y. E.; Lee, K. E.; Kim, H.; Seo, S. K. & Lee, B. S. Urinary vitamin D-binding protein is elevated in patients with endometriosis. Hum. Reprod., 27(2):515–22, 2012.
Christakos, S. & DeLuca, H. F. Minireview: Vitamin D: Is there a role in extraskeletal health? Endocrinology, 152(8):2930-36, 2011.
Dusso, A. S. Kidney disease and vitamin D levels: 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and VDR activation. Kidney Int. Suppl., 1(4):136– 41, 2011.
Dusso, A. S. Renal vitamin D receptor expression and vitamin D renoprotection. Kidney Int., 81(10):937–39, 2012.
Dusso, A. S.; Brown, A.J. & Slatopolsky, E. Vitamin D. Am. J. Physiol. Renal Physiol., 289(1):F8–28, 2005.
Dusso, A. S. & Tokumoto, M. Defective renal maintenance of the vitamin D endocrine system impairs vitamin D renoprotection: a downward spiral in kidney disease. Kidney Int., 79(7):715– 29, 2011.
Ellfolk, M.; Norlin, M.; Gyllensten, K. & Wikvall, K. Regulation of human vitamin D(3) 25- hydroxylases in dermal fibroblasts and prostate cancer LNCaP cells. Mol. Pharmacol., 75(6):1392– 99, 2009.
Fabri, M.; Stenger, S.; Shin, D. M.; Yuk, J. M.; Liu, P. T.; Realegeno, S.; Lee H. M.; Krutzik, S. R.; Schenk, M.; Sieling, P. A.; Teles, R.; Montoya, D.; Iyer S. S.; Bruns, H.; Lewinsohn, D. M.; Hollis, B. W.; Hewison, M.; Adams, J. S.; Steinmeyer, A.; Zügel, U.; Cheng, G.; Jo, E. K.; Bloom, B. R. & Modlin, R. L. Vitamin D is required for IFN-gammamediated antimicrobial activity of human macrophages. Sci. Transl. Med., (104):104ra-102, 2011.
Gao, L.; Tao, Y.; Zhang, L. & Jin, Q. Vitamin D receptor genetic polymorphisms and tuberculosis: updated systematic review and meta-analysis. Int. J. Tuberc. Lung Dis., 14(1):15-23, 2010.
George, P. S.; Pearson, E. R. & Witham, M. D. Effect of vitamin D supplementation on glycaemic control and insulin resistance: a systematic review and meta-analysis. Diabet. Med., 29(8):e142-50, 2012.
Goodarzi, M. O.; Dumesic, D. A.; Chazenbalk, G. & Azziz, R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat. Rev. Endocrinol., 7(4):219–31, 2011.
Guyton, K. Z., Kensler, T. W. & Posner, G. H. Vitamin D and vitamin D analogs as cancer chemopreventive agents. Nutr. Rev.,61(7):227– 38, 2003.
Hammoud, A. O.; Meikle, A. W.; Peterson, C. M.; Stanford, J.; Gibson, M. & Carrell, D.T. Association of 25-hydroxy-vitamin D levels with semen and hormonal parameters. Asian J. Androl., 14 (6):855-59, 2012.
Haussler, M. R.; Whitfield, G. K.; Kaneko, I.; Haussler, C. A.; Hsieh, D.; Hsieh, J. C. & Jurutka, P.W. Molecular mechanisms of vitamin D action. Calcif. Tissue Int., 92(2):77-98, 2013.
Haussler, M. R.; Haussler, C. A.; Whitfield, G. K.; Hsieh, J. C.; Thompson, P. D.; Barthel, T. K.; Bartik, L.; Egan, J. B.; Wu, Y.; Kubicek, J. L.; Lowmiller, C. L.; Moffet, E. W.; Forster, R. E. & Jurutka, P. W. The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the “Fountain of Youth” to mediate healthful aging. J. Steroid. Biochem. Mol. Biol., 121(1–2):88–97, 2010.
Haussler, M. R.; Whitfield, G. K.; Kaneko, I.; Forster, R.; Saini, R.; Hsieh, J. C.; Haussler, C. A. & Jurutka, P. W. The role of vitamin D in the FGF23, klotho, and phosphate bone-kidney endocrine axis. Rev. Endocr. Metab. Disord., 13(1):57-69, 2012.
Haussler, M. R.; Jurutka, P. W.; Mizwicki, M. & Norman, A. W. Vitamin D receptor (VDR)-mediated actions of 1a,25(OH)(2)vitamin D(3): Genomic and nongenomic mechanisms. Best. Pract. Res. Clin. Endocrinol. Metab., 25(4):543–59, 2011.
Henry, H. L. Regulation of vitamin D metabolism. Best. Pract. Res. Clin. Endocrinol. Metab., 25(4):531- 41, 2011.
Hewison, M.; Burke, F.; Evans, K. N.; Lammas, D. A.; Sansom, D. M.; Liu P.; Modlin, R. L. & Adams J. S. Extra-renal 25-hydroxyvitamin D3-1alphahydroxylase in human health and disease. J. Steroid. Biochem. Mol. Biol., 103(3-5):316-21,2007.
Holick, M. F. Vitamin D deficiency. N. Engl. J. Med., 357(3):266–81, 2007.
Jurutka, P. W.; Whitfield, G. K.; Hsieh, J. C.; Thompson, P. D.; Haussler, C. A. & Haussler M. R. Molecular nature of the vitamin D receptor and its role in regulation of gene expression. Rev. Endocr. Metab. Disord., 2(2):203–16, 2001.
Kato, S.; Yoshizazawa, T.; Kitanaka, S.; Murayama, A. & Takeyama, K. Molecular genetics of vitamin D-dependent hereditary rickets. Horm. Res., 57(3–4):73–8, 2002.
Lerchbaum, E. & Obermayer-Pietsch, B. Vitamin D and fertility: a systematic review. Eur. J. Endocrinol., 166(5):765–78, 2012.
Levin, A.; Bakris, G. L.; Molitch, M.; Smulders, M.; Tian, J.; Williams, L. A. & Andress, D. L. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int., 71(1):31-8, 2007.
Lips, P. Vitamin D physiology. Prog. Biophys. Mol. Biol., 92(1):4-8, 2006.
Mahmoudi, A. R.; Zarnani, A. H.; Jeddi-Tehrani, M.; Katouzian, L.; Tavakoli, M.; Soltanghoraei, H. & Mirzadegan, E. Distribution of vitamin D receptor and 1a-hydroxylase in male mouse reproductive tract. Reprod. Sci., 20(4):426-36, 2013.
Maia-Ceciliano, T. C.; Barreto-Vianna, A. R.; Barbosa-da-Silva, S.; Aguila, M. B.; Faria T. S. & Mandarim-de-Lacerda, C. A. Maternal vitamin D-restricted diet has consequences in the formation of pancreatic islet/insulin-signaling in the adult offspring of mice. Endocrine, 2016, en prensa.
Martí, G.; Audí, L.; Esteban, C.; Oyarzábal, M.; Chueca, M.; Gussinyé, M.; Yeste, D.; Fernández-Cancio, M.; Andaluz, P. & Carrascosa, A. Association of vitamin D receptor gene polymorphism with type 1 diabetes mellitus in two Spanish populations. Med. Clin. (Barc.) (123):286-90, 2004.
Mejía, N.; Roman-García, P.; Miar, A. B.; Tavira, B. & Cannata-Andía, J. B. Chronic kidney disease-mineral and bone disorder: a complex scenario. Nefrologia, 31(5):514-9, 2011.
Mora, J. R., Iwata, M. & von Andrian, U. H. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat. Rev. Immunology, 8(9):685-98, 2008.
Moore, W. & Pascual, R. M. Update in asthma 2009.
Am. J. Respir. Crit. Care Med., 181(11):1181-87, 2010.
Morrison, N. A.; Qi, J. C.; Tokita, A.; Kelly, P. J.; Crofts, L.; Nguyen, T. V.; Sambrook, P. N. & Eisman, J. A. Prediction of bone density from vitamin D receptor alleles. Nature, 367(6460):284-87, 1994.
Miyake, Y.; Sasaki, S.; Tanaka, K. & Hirota, Y. Dairy food, calcium and vitamin D intake in pregnancy, and wheeze and eczema in infants. Eur. Respir. J., 35(6):1228-34, 2010.
Parikh, G.; Varadinova, M.; Suwandh, P.; Araki, T.; Rosenwaks, Z.; Poretsky, L. & Seto-Young D. Vitamin D regulates steroidogenesis and insulinlike growth factor binding protein-1 (IGFBP-1) production in human ovarian cells. Horm. Metab. Res., 42(10):754–57, 2010.
Qiao, J. & Feng, H. L. Extra- and intra-ovarian factors in polycystic ovary syndrome: Impact on oocyte maturation and embryo developmental competence. Hum. Reprod. Update., 17(1):17- 33, 2011.
Rojansky, N.; Benshushan, A.; Meirsdorf, S.; Lewin, A.; Laufer, N. & Safran, A. Seasonal variability in fertilization and embryo quality rates in women undergoing IVF. Fertil. Steril., 74(3):476-81, 2000.
Rosen, C. J. Vitamin D Insufficiency. N. Engl. J. Med., 364:248-54, 2011.
Shahbazi, M.; Jeddi-Tehrani, M.; Zareie, M.; SalekMoghaddam, A.; Akhondi, M. M.; Bahmanpoor, M.; Sadeghi, M. R. & Zarnani, A. H. Expression profiling of vitamin D receptor in placenta, decidua and ovary of pregnant mice. Placenta, 32(9):657-64, 2011.
Slatopolsky, E. & Moe, S. 50 years of research and discovery in chronic kidney disease nd mineral & bone disorder: the central role of phosphate. Kidney Int., (121):S1-2, 2011.
Thakkinstian, A.; D'Este C.; Eisman, J.; Nguyen, T. & Attia, J. Meta-analysis of molecular association studies: vitamin D receptor gene polymorphisms and BMD as a case study. J. Bone Miner. Res., 19(3):419-28, 2004.
Uitterlinden, A. G.; Fang, Y.; Van Meurs, J. B.; Pols, H. A. & Van Leeuwen, J. P. Genetics and biology of vitamin D receptor polymorphisms. Gene, 338(2):143-56, 2004.
Velarde Félix, J. S.; Cázarez Salazar, S. G.; Castro Velázquez, R.; Rendón Maldonado, J. G. & Rangel Villalobos, H. Relación del polimorfismo TaqI del gen del receptor de la vitamina D con la lepra lepromatosa en población mexicana. Salud Publica Mex., 51(1):59-61, 2009.
Vilarino, F. L.; Bianco, B.; Christofolini, D. M.; Lerner, T. G. & Barbosa, C. P. Analysis of vitamin D receptor gene polymorphisms in women with and without endometriosis. Rev. Bras. Ginecol. Obstet., 33(2):65-9, 2011.
Zhang, J.; Li, W.; Liu, J.; Wu, W.; Ouyang, H.; Zhang, Q.; Wang, Y.; Liu, L.; Yang, R.; Liu, X; Meng, Q. & Lu, J. Polymorphisms in the vitamin D receptor gene and type 1 diabetes mellitus risk: An update by meta-analysis. Mol. Cell. Endocrinol., 355(1):135-42, 2012.