Vitamin D

Vitamin D: The Calcium Homeostatic Steroid Hormone provides a continuing coordinated group of edited critiques of the dynamic state of the science and art of nutrition. The most recent basic advances will be reviewed within the broad framework of the scientific knowledge of food and nutrition, including its application to man, individually and societally. The volumes, authored singly or by invited contributors, will appeal to serious scholars concerned with pure or applied nutrition.
This volume comprises 13 chapters, with the first discussing the progress of vitamin D-cholecalciferol from vitamin to steroid hormone. Succeeding chapters then discuss the biological and chemical assay of vitamin D, its metabolites, and analogs; metabolism of vitamin D; and the tissue and subcellular localization of vitamin D and its metabolites. Other chapters cover binding proteins and receptors for vitamin D and its metabolites; interrelationships between vitamin D and other hormones; intestinal effects of vitamin D; vitamin D actions in the kidney; vitamin D actions on bone; and vitamin D and its clinical relationships. This book will be of interest to practitioners in the fields of chemistry, nutrition, and medicine.

Foreword

Preface

Chapter 1 Vitamin D-Cholecalciferol: from Vitamin to Steroid Hormone

I. Historical Review

A. Opening Comments

B. History

II. The Present (1960 to 1979)

A. Biological Facts Related to Vitamin D

?. The Steroid Hormone Mode of Action of Vitamin D

References

Chapter 2 The Provitamins D

I. Background Considerations

A. Definition of a Provitamin

B. Identification of the Concept of a Provitamin

C. Chemical Characterization of Provitamins

II. Occurrence

III. Chemistry

A. Structural Requirement for Activity

B. Chemical Synthesis

References

Chapter 3 The Vitamins D

I. Background Considerations

A. Minimal Structural Requirements for Activity

B. Chemical Characterization

II. Natural Occurrence of Vitamins D

III. Chemistry of Vitamins D

A. Structure and Physical Properties of Vitamin D and Related Steroids

B. Conformation

C. Photochemical Production

D. Chemical Synthesis

E. Synthesis of Radioactive Vitamin D and Metabolites

F. Industrial Production of Vitamin D

IV. Methods of Chromatographic Separation of Vitamin D Compounds

References

Chapter 4 Biological and Chemical Assay of Vitamin D, Its Metabolites, and Analogs

I. Introduction

A. Types of Methods and Their Sensitivity

B. Definition and Standardization of Activity

II. Biological Determinations

A. Official Assays

B. Other Assays

III. Chemical Determinations

A. Ultraviolet Absorption

B. Colorimetric Methods

C. Gas Chromatography

D. Gas Chromatography-Mass Spectrometry

E. High-Pressure Liquid Chromatography

IV. Summary

References

Chapter 5 Vitamin D Metabolites and Analogs

I. Introduction

A. Metabolism of Vitamin D

B. Opportunity for Structure-Function Studies

II. Isolation, Characterization, and Chemical Synthesis of Vitamin D Metabolites

A. 25(OH)D3

B. 25(OH)D2

C. 1,25(OH)2D3

D. 1,25(OH)2D2

E. 24,25(OH)2D3

F. 1,24,25(OH)3D3

G. 25,26(OH)2D3

H. 1-(OH)-24,25,26,27-Tetranor-23-COOH-D3

I. 25-(OH)-26,23-Lactone-D3

J. 25,26,27-Trinor-24-COOH-D3

III. Analogs of Vitamin D and Its Metabolites

A. General Considerations

B. ?-Ring Analogs

C. Side-Chain Analogs

D. Other Analogs Related to Vitamin D

IV. Structure-Function Studies

A. Problems of Evaluation

B. Structural Features Required for Optimization of Vitamin D Activity

C. Possible Relationship of Steroid Conformation to Biological Activity

D. Analog Studies

References

Chapter 6 Metabolism of Vitamin D

I. Introduction

A. Background

B. Discovery of Vitamin D Metabolism

II. Vitamin D

A. Photochemical Production

B. Possible Nonphotochemical Production

C. Intestinal Absorption

D. Vitamin D 25-Hydroxylase

III. 25-Hydroxyvitamin D

A. 25-Hydroxyvitamin D 1-Hydroxylase

B. 25-Hydroxyvitamin D 24-Hydroxylase

C. Production of 1,24,25(OH)3D3

D. Integrated Regulation of the Renal Metabolism of 25(OH)D3

E. Production of 25,26(OH)2D3

IV. 1,25(OH)2D3 Metabolism: Unresolved Problems

V. Vitamin D Metabolism in Man

VI. Metabolism of Vitamin D Analogs

A. 1 ?-Hydroxy vitamin D3

B. Pseudo 1?-Analogs

VII. Effects of Chlorinated Hydrocarbons on Vitamin D Metabolism

References

Chapter 7 The Tissue and Subcellular Localization of Vitamin D and Its Metabolites: a Basis for Their Hormonal Mode of Action

I. Tissue Distribution Studies

A. Early Studies (Prior to 1960)

B. Modern Studies (after 1960)

II. Subcellular Distribution Studies

A. Intestinal Mucosa

B. Bone

C. Parathyroid Gland

D. Other Organs (Kidney, Liver, Brain)

III. Intestinal Nuclear Localization of l,25(OH)2D3 as a Basis for Its Steroid Hormone Mode of Action

A. Lag in Action of Vitamin D and 1,25(OH)2D3

B. Effects of Actinomycin D and Other Antibiotics on Intestinal Calcium Absorption

C. Molecular Basis of Steroid Hormone Mode of Action of 1,25(OH)2D3

D. Effects of Vitamin D and 1,25(OH)2D3 on RNA Metabolism

E. Effects of Vitamin D and 1,25(OH)2D3 on Protein Synthesis

IV. Summary

References

Chapter 8 Binding Proteins and Receptors for Vitamin D and Its Metabolites

I. Vitamin D

A. Binding Proteins

B. Competitive Binding Assay

II. 25(OH)D

A. Binding Proteins

B. Competitive Binding Assays

III. 1,25(OH)2D

A. Binding Proteins

B. Competitive Binding Assays

IV. 24,25(OH)2D Assay

V. Bone Calvaria Assay for Vitamin D Metabolites

References

Chapter 9 Interrelationships between Vitamin D and Other Hormones

I. Introductory Comments

A. Physiological Roles of Vitamin D, Parathyroid Hormone, and Calcitonin

B. Dynamics and Requirements of Calcium and Phosphate Metabolism

II. Parathyroid Hormone and Calcitonin

A. Effects of Parathyroid Hormone on Vitamin D Metabolism

B. Effects of Vitamin D Metabolites on Parathyroid Gland

C. Calcitonin

D. Integrated View of Calcium Homeostasis

III. Adrenal Cortical Steroids

A. Background

B. Hydrocortisone-Parathyroid Hormone Interaction

C. Hydrocortisone Inhibition of Intestinal Calcium Absorption

D. Effects of Glucocorticoids on Vitamin D Metabolism

IV. Other Hormones

A. Estrogens

B. Thyroxine

C. Growth Hormone-Somatomedin

D. Insulin

E. Prolactin

References

Chapter 10 Intestinal Effects of Vitamin D

I. Background Considerations

A. Introduction

B. Intestinal Morphology and Cytology

C. Intestinal Calcium and Phosphorus Absorption-The Problem

D. Methods of Study

II. Early Work on the Intestinal Absorption of Calcium and Phosphorus

III. Modern Era

A. Adaptation of Intestinal Ca2+ Absorption

B. Contrasting Views on the Mechanism of Calcium and Phosphorus Transport

C. Factors That Affect Intestinal Absorption of Calcium and Phosphorus

D. Effects of Plant Extracts

E. Use of the Polyene Antibiotic Filipin as a Tool to Study Calcium Transport

F. Calcium-Binding Protein

G. Alkaline Phosphatase, ATPase, and Phytase

H. Concluding Remarks

References

Chapter 11 Vitamin D Actions in the Kidney (excluding Vitamin D Metabolism)

I. The Kidney and Mineral Homeostasis

A. Introductory Comments

B. Role of the Kidney and Vitamin D in Calcium and Phosphorus Homeostasis

II. Effects of Vitamin D and Metabolites on Renal Tubular Function

A. Calcium-Binding Protein

B. Calcium

C. Phosphate

D. Other Ions (Na+, HCO3-, K+)

E. Amino Acids

III. Other Vitamin D-Kidney Interactions

A. Mitochondrial Ion Transport

B. Vitamin D and Citric Acid Metabolism

IV. Toxic Effects of Vitamin D on the Kidney

References

Chapter 12 Vitamin D Actions on Bone

I. Background Considerations

A. Introduction

B. Calcium and Phosphorus Homeostasis-Role of the Bone

C. Bone Tissue-Morphology and Physiology

D. The Problem

II. Effects on Bone Collagen

III. Effects on Bone Mineral Metabolism

A. Bone Accretion

B. Bone Resorption

C. Morphological and Histological Alterations

IV. Effects on Bone Organic Acid Metabolism

V. Differential Actions of Vitamin D Metabolites

References

Chapter 13 Vitamin D and Its Clinical Relationships

I. Introduction

A. Background

B. Serum Levels of Vitamin D and Its Metabolites and Their Rates of Production and Turnover

C. Normal Man and Vitamin D

D. Etiology of Clinical Disorders That May Be Related to Vitamin D

E. Clinical Applications of Vitamin D Metabolites

II. Human Disease States Related to Vitamin D

A. Liver

B. Kidney

C. Parathyroid

D. Thyroid

E. Intestinal Relationships

F. Bone

III. Animal Health Applications

A. Poultry Nutrition

B. Postparturient Paresis (Milk Fever)

References

Appendix

A. Molecular Weights, Units and Mole-Equivalents for Vitamin D, Its Metabolites, and Important Analogs

B. Diets Used to Raise Vitamin D-Deficient Animals

C. IUPAC Nomenclature Rules for Vitamin D

D. Bibliography: Review Articles and Books Related to Vitamin D

Subject Index