Vitamin D Hormone

 
 
Academic Press
  • 1. Auflage
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  • erschienen am 30. Januar 2016
  • |
  • 502 Seiten
 
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978-0-12-805240-2 (ISBN)
 

First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press.

The Series provides up-to-date information on vitamin and hormone research spanning data from molecular biology to the clinic. A volume can focus on a single molecule or on a disease that is related to vitamins or hormones. A hormone is interpreted broadly so that related substances, such as transmitters, cytokines, growth factors and others can be reviewed.

This volume focuses on vitamin D hormone.


  • Expertise of the contributors
  • Coverage of a vast array of subjects
  • In depth current information at the molecular to the clinical levels
0083-6729
  • Englisch
  • San Diego
  • |
  • USA
Elsevier Science
  • 33,52 MB
978-0-12-805240-2 (9780128052402)
0128052406 (0128052406)
weitere Ausgaben werden ermittelt
  • Front Cover
  • Vitamin D Hormone
  • Copyright
  • Former Editors
  • Contents
  • Contributors
  • Preface
  • Chapter One: Vitamin D: Historical Overview
  • 1. The Discovery of Vitamin D
  • 2. The Discovery of the Physiological Functions of Vitamin D
  • 3. The Discovery of the Hormonal Form of Vitamin D
  • 4. The Isolation of the Final Active Form of Vitamin D
  • 5. Discovery of the Vitamin D Endocrine System (Fig.5)
  • 6. Other Metabolism of Vitamin D
  • 7. Discovery of the Vitamin D Receptor
  • References
  • Chapter Two: Genomic Determinants of Vitamin D-Regulated Gene Expression
  • 1. Introduction
  • 2. Genome-Wide Analysis Reveals New Concepts in Vitamin D Action
  • 3. Novel Principles of Vitamin D Action
  • 3.1. Modes of DNA Binding and Implications for the Regulatory Activity of the VDR
  • 3.1.1. Ligand-Independent Function of the VDR in the Hair Cycle
  • 3.1.2. Ligand-Independent Suppression of Gene Expression by the VDR
  • 3.2. 1,25(OH)2D3 Regulates Transcription via Multiple Enhancers Located at Sites Distal to Gene Promoters
  • 3.2.1. Defining Gene Regulation from Distal Sites
  • 3.2.2. Confirming Enhancer Function at Target Genes
  • 3.2.3. Application of the CRISPR/Cas9 Method to the Study of Gene Regulation
  • 4. The Influence of Cellular Differentiation on Vitamin D Activity
  • 4.1. Differentiation Is Accompanied by Direct Alterations in the VDR Cistrome
  • 4.2. The Impact of Osteoblast Differentiation on Master Regulatory Factor Distribution, Histone Modifying Activity, and R ...
  • 4.3. Identification and Structure of the Osteoblast Enhancer Complex
  • 5. VDR Modulates Histone Acetylation at Target Genes
  • 6. Summary
  • Acknowledgments
  • References
  • Chapter Three: Inhibitors for the Vitamin D Receptor-Coregulator Interaction
  • 1. Introduction
  • 1.1. VDR Coactivators
  • 1.2. VDR Corepressors
  • 2. Peptide-Based Inhibitors of the VDR-Coregulator Interaction
  • 3. Small-Molecule Inhibitors of the VDR-Coregulator Interaction
  • 4. VDR Antagonists or Allosteric Inhibition of the VDR-Coregulators Interaction
  • 4.1. TEI-9647
  • 4.2. ZK159222
  • 4.3. ZK168281
  • 4.4. ZK191784
  • 4.5. Amide-Based VDR Antagonists
  • 4.6. Adamantane-Based VDR Antagonists
  • 4.7. Branched VDR Antagonists
  • 5. Conclusion and Future Directions
  • Acknowledgments
  • References
  • Chapter Four: Structural Studies of Vitamin D Nuclear Receptor Ligand-Binding Properties
  • 1. Introduction
  • 2. Crystal Structures of VDR LBD in Complex with 1,25(OH)2D3
  • 2.1. Overall Organization of Human, Rat, and Zebrafish VDR-LBD Complexes
  • 2.2. Activation Function-2
  • 2.3. Recognition of Coactivator Peptide
  • 2.4. VDR Ligand-Binding Pocket
  • 3. Secosteroidal Derivatives of 1,25(OH)2D3
  • 3.1. Superagonists of VDR
  • 3.1.1. 20-Epi Derivatives
  • 3.1.2. C2-Substituted Analogs
  • 3.1.3. 14-Epi Analogs
  • 3.2. Synthetic Compounds Expanding the VDR LBP
  • 3.2.1. Gemini Analogs
  • 3.2.2. 22-Alkyl Derivatives
  • 3.2.3. Adamantyl-Containing Compounds
  • 4. Synthetic Mimics of 1,25(OH)2D3
  • 4.1. Derivatives of LG190178
  • 4.2. Bis- and Tris-Aromatic Compounds
  • 4.3. Compounds with p-Carborane Core
  • 5. Crystal Structures of VDR LBD with Lithocholic Acid
  • 5.1. Crystal Structures of rVDR LBD with LCA and Its Derivatives
  • 5.2. Crystal Structure of zVDR LBD with LCA: Alternative LCA-Binding Site
  • 6. Crystal Structures of HVDRR-Associated VDR Mutants
  • 6.1. His305Gln VDR Mutant
  • 6.2. Arg274Leu VDR Mutant
  • 6.3. Trp286Arg VDR Mutant
  • 7. Dynamic Process of Ligand Binding
  • 8. Conclusion and Perspectives
  • Acknowledgments
  • References
  • Chapter Five: Crystal Structure of the Vitamin D Receptor Ligand-Binding Domain with Lithocholic Acids
  • 1. Introduction
  • 2. Lithocholic Acids
  • 3. Structures of the VDR LBD with LCAs
  • 3.1. Structures of the Ternary Complexes
  • 3.2. Structures of the Ligands and Their Interactions with VDR-LDB
  • 4. Mechanism of Agonist Activities of LCA to VDR
  • 5. Conclusions and Future Directions
  • References
  • Chapter Six: 25-Hydroxyvitamin D3 24-Hydroxylase: A Key Regulator of 1,25(OH)2D3 Catabolism and Calcium Homeostasis
  • 1. Introduction and Catalytic Properties
  • 2. CYP24A1 Gene and Crystal Structure of CYP24A1
  • 3. Cyp24a1-Null Mice
  • 4. Genetic Defect in CYP24A1: A Cause of Idiopathic Infantile Hypercalcemia
  • 5. Regulation of CYP24A1
  • 6. Aging and CYP24A1
  • 7. Placental CYP24A1
  • 8. Genomic Mechanisms Mediating 1,25(OH)2D3 Regulation of CYP24A1
  • 9. Conclusion and Future Directions
  • Acknowledgment
  • References
  • Chapter Seven: Analogs of 1a,25-Dihydroxyvitamin D3 in Clinical Use
  • 1. Discovery of the Vitamin D Endocrine System
  • 2. Vitamin D Metabolites
  • 2.1. 25-Hydroxyvitamin D3
  • 2.2. 1a,25-Dihydroxyvitamin D3
  • 3. Precursors to 1,25-Dihydroxyvitamin D3
  • 3.1. 1a-Hydroxyvitamin D3 (1a-OH-D3, Alfacalcidol)
  • 3.2. 1a-Hydroxyvitamin D2 (1a-OH-D2, Doxercalciferol)
  • 4. Analogs of 1,25-Dihydroxyvitamin D3
  • 4.1. 22-Oxa-1a,25-Dihydroxyvitamin D3 (Oxacalcitriol)
  • 4.2. MC903 or Calcipotriol
  • 4.3. [2ß-(3-Hydroxypropoxy)-1a,25-Dihydroxyvitamin D3] (ED-71)
  • 4.4. 26,27-Hexafluoro-1a,25-Dihydroxyvitamin D3 (Falecalcitriol)
  • 4.5. 19-Nor-1a,25-Dihydroxyvitamin D2 (Paricalcitol)
  • 5. Functions of Vitamin D Beyond Bone, Parathyroid, Calcium, and Phosphorus
  • References
  • Chapter Eight: 1,25-Dihydroxyvitamin D and Klotho: A Tale of Two Renal Hormones Coming of Age
  • 1. Introduction
  • 2. 1,25-Dihydroxyvitamin D
  • 2.1. Synthesis and Degradation
  • 2.2. Nuclear Receptor-Mediated Mechanism of Ligand Action
  • 2.3. Target Genes
  • 2.4. Impact on Disease
  • 2.4.1. Bone Mineral Metabolism (Osteoporosis)
  • 2.4.2. Detoxification and Antioxidation (Healthspan/Senescence)
  • 2.4.3. Neuropsychiatric Disorders (ADHD, Autism, Bipolar Disorder, Depression, Schizophrenia
  • Antisocial, Obsessive-Compu ...
  • 2.4.4. Skin (Hair Loss and Psoriasis)
  • 2.4.5. Cancer Prevention (Epithelial and Blood Cell Malignancies)
  • 2.4.6. Metabolism (Obesity)
  • 2.4.7. Cardiovascular Disease (Hypertrophy, Fibrosis, and Vascular Calcification)
  • 3. Klotho
  • 3.1. Membrane and Secreted Forms
  • 3.2. Coreceptor Function of Membrane Klotho: Feedback Control of Phosphate and Vitamin D Metabolism
  • 3.3. Calcium Metabolism and Antioxidation
  • 3.4. Effects on Wnt Signaling: Antifibrotic and Anticancer Actions
  • 3.5. Influence on Insulin/IGF-1 Actions
  • 3.6. Anti-aging and Organ Protection
  • 4. Conclusion and Future Directions
  • Acknowledgments
  • References
  • Chapter Nine: Hedgehog and Vitamin D Signaling Pathways in Development and Disease
  • 1. The Hedgehog Signaling Pathway
  • 1.1. Hedgehog Signal Transduction
  • 1.2. Hh Signaling in Cancer
  • 1.3. Mechanisms of Resistance to Hh Signaling
  • 2. Vitamin D Metabolism and Regulation
  • 3. Vitamin D/Hh Pathway Regulation in the Skin
  • 3.1. Vitamin D Control Over Skin Differentiation
  • 3.2. Tumor Suppressor Properties of Calcitriol/VDR in Skin
  • 3.3. Vitamin D/VDR in BCC Development
  • 4. Inhibition of Hh Signaling by Vitamin D-Based Small Molecules
  • 4.1. Natural Vitamin D Ligands
  • 4.1.1. Vitamin D3/Cholecalciferol
  • 4.1.2. Calcitriol
  • 4.2. Synthetic Vitamin D Analogues
  • 4.3. Cellular Mechanisms that Govern Hh Inhibition for Vitamin D-Based Seco-Steroids
  • 5. Discussion and Conclusions
  • References
  • Chapter Ten: Molecular Approaches for Optimizing Vitamin D Supplementation
  • 1. Introduction
  • 2. A View from Evolution
  • 3. Vitamin D and the Epigenome
  • 4. Molecular Insight from Vitamin D Intervention Trials
  • 5. Consequences for Vitamin D Supplementation
  • 6. Conclusion and Future Directions
  • Acknowledgments
  • References
  • Chapter Eleven: The Role of Vitamin D3 in the Development and Neuroprotection of Midbrain Dopamine Neurons
  • 1. Introduction
  • 2. Biosynthesis and Metabolism of Vitamin D3
  • 2.1. Source, Storage, and the Blood-Brain Barrier
  • 2.2. Metabolism to Calcitriol and Other Active Metabolites
  • 2.3. Physiological Activity/Levels
  • 3. Vitamin D3 and Health
  • 3.1. Bone Health
  • 3.2. Back Pain
  • 3.3. Cancer
  • 3.4. Immunity
  • 3.5. Vitamin D Toxicity (Hypervitaminosis D)
  • 4. Vitamin D3 in the Central Nervous System
  • 4.1. Multiple Sclerosis
  • 4.2. Depression, Mental Health, and Cognitive Function
  • 4.3. Vitamin D in CNS Development
  • 5. Vitamin D and Neuroprotection in Parkinson´s Disease
  • 5.1. Population-Based Evidence Linking Vitamin D and Parkinson´s Disease
  • 5.2. In vitro Evidence of Neuroprotective Properties of Vitamin D
  • 5.3. Neuroprotection by Vitamin D in vivo
  • 5.4. Clinical Studies with Vitamin D and Parkinson´s Disease
  • 6. Future Developments and Applications to Parkinson´s Disease
  • References
  • Chapter Twelve: Vitamin D and Cardiac Differentiation
  • 1. Introduction
  • 2. Calcitriol and CVD
  • 3. Calcitriol Is Critical in the Modulation and Maintenance of Heart Cell Structure and Function
  • 3.1. VDR Involved in Cardiovascular System
  • 3.2. 1,25-D3 Actions on HL-1 Cardiac Myocyte
  • 4. Noncanonical Wnt11 Signaling and Cardiogenesis
  • 5. 1,25-Vitamin D3 Promotes Cardiac Differentiation Through Modulation of the Wnt Signaling Pathway
  • 5.1. 1,25-D3 Inhibits Cell Proliferation of H9c2 Cardiomyocytes
  • 5.2. 1,25-D3 Enhances Cardiomyotube Area and Promotes the Expression of Cardiac Troponin
  • 5.3. 1,25-D3 Induces Cell Cycle Exit of H9c2 Cardiac Cells, Without Inducing Apoptosis
  • 5.4. 1,25-D3 Modulates the Expression of Key Components of the Canonical and Noncanonical Wnt Signaling Pathway
  • 6. Regulation of Cardiac Function Through Inhibition of Wnt Signaling Pathway
  • 7. Conclusion and Future Directions
  • References
  • Chapter Thirteen: Vitamin D in Prostate Cancer
  • 1. Introduction
  • 2. Vitamin D Metabolism: Synthesis, Degradation, Relevance to Prostate Cancer
  • 2.1. Enzymatic Machinery for Vitamin D Biosynthesis and Degradation
  • 2.2. Vitamin D Metabolism in Prostate Cancer
  • 3. VDR-Regulated Gene Transcription: Ligand Specificity, DNA Response Elements, Domain-Induced Allostery
  • 3.1. DNA Response Elements
  • 3.2. Domain-Induced Allostery
  • 4. Inhibition of Prostate Cancer by Vitamin D: Insights from Cell Culture and Preclinical Studies, and Clinical Trials
  • 4.1. Mechanisms for Antiproliferative Actions
  • 4.1.1. Cell Cycle Arrest
  • 4.1.2. Differentiation
  • 4.1.3. Apoptosis
  • 4.1.4. Angiogenesis, Cell Migration, Metastasis
  • 4.2. Preclinical Studies
  • 4.3. Tumor-Expressed VDR, Association with Lethal Cancer, Clinical Potential of Vitamin D
  • 5. Functional Interplay of AR and VDR in Prostate Cancer: Impact on Cell Growth and Intracrine Androgen Biosynthesis
  • 5.1. Impact on Cell Growth
  • 5.2. Calcitriol, Androgen, and Intracrine Androgen Metabolism in Prostate
  • 6. Summary and Future Possibilities
  • Acknowledgments
  • References
  • Chapter Fourteen: Metabolism and Action of 25-Hydroxy-19-nor-Vitamin D3 in Human ProstateCells
  • 1. Introduction
  • 2. The Chemistry and Synthetic Schemes for 25-Hydroxy-19-nor-Vitamin D3
  • 3. 19-nor-Vitamin D3 Analogs as Therapeutic Agent for Human ProstateCancer
  • 3.1. Vitamin Dand ProstateCancer
  • 3.2. The Biological Activity of 19-nor-Vitamin DAnalogs
  • 4. The Biological Activities of 25-Hydroxy-19-nor-Vitamin D3
  • 4.1. The Translocation of VDR into the Nucleus
  • 4.2. The Transcriptional Activation of CYP24A1Gene
  • 4.3. The Antiproliferative Effect of 25(OH)-19-nor-D3 in the Human ProstateCells
  • 5. The Metabolism of 25-Hydroxy-19-nor-Vitamin D3 in ProstateCells
  • 5.1. 25(OH)-19-nor-D3 is Hardly Subjected to 1a-Hydroxylation
  • 5.2. Cellular Metabolism of 25(OH)-19-nor-D3
  • 6. Novel Mechanism of Action of 25-Hydroxy-19-nor-Vitamin D3
  • 7. Conclusions and Future Directions
  • References
  • Chapter Fifteen: Vitamin D Analogs with Nitrogen Atom at C2 Substitution and Effect on Bone Formation
  • 1. Introduction
  • 2. Synthesis of New VDR Ligands: (Heteroaryl)ethyl Group at C2a
  • 2.1. Tetrazole
  • 2.2. Triazole
  • 2.2.1. 1,2,4-Triazole
  • 2.2.2. 1,2,3-Triazole
  • 2.3. Imidazole
  • 3. Synthesis of New VDR Ligands: Cyanoalkyl or Cyanoalkoxy Group at C2a and C2ß
  • 4. Biological Activity of New VDR Ligands
  • 4.1. hVDR Binding Affinity and Transcriptional Activity
  • 4.2. In Vivo Effects on Bone Mineral Density
  • 5. New Ligands Bound to hVDR: X-Ray Cocrystallographic Analyses
  • 6. Summary
  • Acknowledgments
  • References
  • Chapter Sixteen: Mechanistic Insights of Vitamin D Anticancer Effects
  • 1. Overview of Vitamin D Anticancer Effects
  • 2. Epidemiological Studies
  • 3. Experimental Studies
  • 3.1. Antitumor Activity and Mechanisms of Vitamin D as a Single Agent
  • 3.2. Proliferation
  • 3.3. Apoptosis
  • 3.4. Differentiation
  • 3.5. Angiogenesis
  • 3.6. Invasion and Metastasis
  • 3.7. Inflammation
  • 3.8. 1,25D3 in Combinational Treatment
  • 4. Conclusions
  • Acknowledgments
  • References
  • Chapter Seventeen: Vitamin D Signaling Modulators in Cancer Therapy
  • 1. Introduction
  • 2. Vitamin D Receptor and 1,25D3 Signaling
  • 3. Glucocorticoid, 1,25D3-Mediated Antitumor Effect and Hypercalcemia
  • 4. GR and VDR Signaling
  • 5. Regulation of CYP24A1 Expression
  • 6. CYP24A1 Expression in Cancer
  • 7. CYP24A1 Inhibitors
  • 8. Vitamin D Analogs
  • 9. Conclusions
  • References
  • Index
  • Color Plate
  • Back Cover

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