ویتامین D: مرور تاریخی

A history of vitamin D has been provided, dating from the earliest description of rickets, the disease resulting from vitamin D deficiency, to a current understanding of vitamin D metabolism and the mechanism of action of its hormonal form in regulating gene expression in target organs. Vitamin D is produced in skin by impact of 280-310 nm light on 7-dehydrocholesterol. The vitamin D is then converted in the liver to a circulating form, 25-hydroxyvitamin D that is converted largely, if not exclusively, in the kidney to the final hormone, 1α,25-dihydroxyvitamin D. This hormone functions through a nuclear receptor that regulates expression of key genes in target organs. Among its many resulting functions are increased intestinal calcium and phosphate absorption, bone calcium mobilization, and renal reabsorption of calcium. The resultant increase in serum calcium and phosphate supports bone mineralization, curing rickets, and osteomalacia. There are many other functions of vitamin D that remain to be described that contribute to its health supporting role. Content: 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 Action3. 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 Regulation4. 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. Introduction1.1. 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. Introduction2. 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

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

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