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Vitamin D signaling is modulated on multiple levels in health and disease.
Mol Cell Endocrinol 2006; 248(1-2):149-59MC

Abstract

Vitamin D signaling is dependent on the availability and turnover of the active Vitamin D receptor (VDR) ligand 1,25-dihydroxycholecalciferol and on the efficiency of VDR transactivation. Activating and inactivating secosteroid metabolizing p450 enzymes, e.g. 25-hydroxylases, 1alpha-hydroxylase and 24-hydroxylase, are responsible for ligand availability on the basis of substrate production in the skin and of nutritional intake of precursors. Net availability of active hormone depends on the delivery of substrate and the balance of activating and inactivating enzymes. 1Alpha-hydroxylase is the critical activating enzyme. It is expressed in the kidney for systemic supply and in target tissues for local secosteroid activation. It is upregulated in the kidney by low calcium intake and parathyroid hormone, downregulated by phosphatonins and proinflammatory signal transduction. Transactivation of VDR depends on the correct molecule structure, effective nuclear translocation and the presence of the unliganded heterodimer partner retinoid X-receptor (RXR) and other nuclear cofactors. Rapid Vitamin D-dependent membrane associated effects and consecutive second messenger activation exert an own pattern of gene regulation. A membrane receptor for these effects is hypothesized but not yet identified. Rickets is the long known clinical syndrome of impaired Vitamin D signaling due to Vitamin D3 deficiency. It can be caused by inherited defects of the cascade, nutritional deficits, lack of sunlight exposure, malabsorption and underlying diseases like chronic inflammation. It has been shown during the last decades that many modifiers of Vitamin D signaling are targets of disease in terms of inherited and acquired syndromes and that Vitamin D signaling is modulated at multiple levels and is more complex than mere mechanistic ligand/receptor/DNA interaction.

Authors+Show Affiliations

Musculosceletal Research Center, Orthopedic Department, University of Wuerzburg, Brettreichstrasse 11, D-97074 Wuerzburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

16406653

Citation

Ebert, Regina, et al. "Vitamin D Signaling Is Modulated On Multiple Levels in Health and Disease." Molecular and Cellular Endocrinology, vol. 248, no. 1-2, 2006, pp. 149-59.
Ebert R, Schütze N, Adamski J, et al. Vitamin D signaling is modulated on multiple levels in health and disease. Mol Cell Endocrinol. 2006;248(1-2):149-59.
Ebert, R., Schütze, N., Adamski, J., & Jakob, F. (2006). Vitamin D signaling is modulated on multiple levels in health and disease. Molecular and Cellular Endocrinology, 248(1-2), pp. 149-59.
Ebert R, et al. Vitamin D Signaling Is Modulated On Multiple Levels in Health and Disease. Mol Cell Endocrinol. 2006 Mar 27;248(1-2):149-59. PubMed PMID: 16406653.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D signaling is modulated on multiple levels in health and disease. AU - Ebert,Regina, AU - Schütze,Norbert, AU - Adamski,Jerzy, AU - Jakob,Franz, Y1 - 2006/01/09/ PY - 2006/1/13/pubmed PY - 2006/6/1/medline PY - 2006/1/13/entrez SP - 149 EP - 59 JF - Molecular and cellular endocrinology JO - Mol. Cell. Endocrinol. VL - 248 IS - 1-2 N2 - Vitamin D signaling is dependent on the availability and turnover of the active Vitamin D receptor (VDR) ligand 1,25-dihydroxycholecalciferol and on the efficiency of VDR transactivation. Activating and inactivating secosteroid metabolizing p450 enzymes, e.g. 25-hydroxylases, 1alpha-hydroxylase and 24-hydroxylase, are responsible for ligand availability on the basis of substrate production in the skin and of nutritional intake of precursors. Net availability of active hormone depends on the delivery of substrate and the balance of activating and inactivating enzymes. 1Alpha-hydroxylase is the critical activating enzyme. It is expressed in the kidney for systemic supply and in target tissues for local secosteroid activation. It is upregulated in the kidney by low calcium intake and parathyroid hormone, downregulated by phosphatonins and proinflammatory signal transduction. Transactivation of VDR depends on the correct molecule structure, effective nuclear translocation and the presence of the unliganded heterodimer partner retinoid X-receptor (RXR) and other nuclear cofactors. Rapid Vitamin D-dependent membrane associated effects and consecutive second messenger activation exert an own pattern of gene regulation. A membrane receptor for these effects is hypothesized but not yet identified. Rickets is the long known clinical syndrome of impaired Vitamin D signaling due to Vitamin D3 deficiency. It can be caused by inherited defects of the cascade, nutritional deficits, lack of sunlight exposure, malabsorption and underlying diseases like chronic inflammation. It has been shown during the last decades that many modifiers of Vitamin D signaling are targets of disease in terms of inherited and acquired syndromes and that Vitamin D signaling is modulated at multiple levels and is more complex than mere mechanistic ligand/receptor/DNA interaction. SN - 0303-7207 UR - https://www.unboundmedicine.com/medline/citation/16406653/Vitamin_D_signaling_is_modulated_on_multiple_levels_in_health_and_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0303-7207(05)00442-9 DB - PRIME DP - Unbound Medicine ER -