Vitamin D : a pluripotent steroid hormone : structural studies, molecular endocrinology, and clinical applications : proceedings of the ninth Workshop on Vitamin D, Orlando, Florida (USA), May 28-June 2, 1994

FOREWORD Official Sponsors and Donors YOUNG INVESTIGATOR AWARDEES NINTH WORKSHOP ON VITAMIN D Vitamin D Workshop. Career Recognition Awardees Contents Chemistry of Vitamin D Shape and Conformation of Vitamin D. 11-Fluoro-1a-Hydroxyvitamin D 3 : The Quest for Experimental Evidence of the Folded Vitamin D Conformation Conformation and Related Topological Features of Vitamin D: Structure-Function Relationships Chemical Conversion of Vitamin D 3 to Calcitriol Lactone Design, Synthesis, and SAR of Some 1-Substituted A-Ring Analogs of Calcitriol A General Synthetic Route to A-Ring Hydroxylated Vitamin D Analogs from D-Pentoses Retiferols. Design and Synthesis of the New Class of Vitamin D Analogs Introduction of 1a-Hydroxyl Group to Provitamin D Causes New Photoisomerization Reactions Synthesis and Determination of the Configurations of the 23-Hydroxylated Metabolites of Calcipotriol (MC 903) and their Epimers Syntheses of Potential Inhibitors of 25-Hydroxyvitamin D 3 -1a-Hydroxylase: A-Ring Analogs Metallic Complexes of Hydroxylated Derivatives of Vitamin D 3 A New Route to the Lythgoe-Roche's A-Ring Precursor of 1a,25-Dihydroxyvitamin D 3 Structure-Activity Studies of Fluorinated Vitamin D Analogs An In Vitro Model of Previtamin D Photosynthesis as Possible Monitor of Ozone Depletion Synthesis of 24-Hydroxy-Vitamin D Analogues Chromatographic Isolation and Spectroscopic Characterization of the Photoisomers of 1a,25-Dihydroxy-Provitamin D 3 A New Route to the Vitamin D Triene System Studies on the Synthesis of 19-Norprevitamin D 3 Analogues Structure/Function Studies of Vitamin D Steroids The Need for New Vitamin D Analogues: Mechanisms of Action and Clinical Applications Future Prospects for Vitamin D Analogs Chemistry and Biology of 22,23-yne Analogs of Calcitriol Chemistry and Biology of 23-oxa-aro- and 23-thia-aro-Vitamin D Analogues with High Antiproliferative and Low Calcemic Activity Activity of Vitamin D Analogs in Co-Transfected COS-7 Cells Synthesis and Biological Character of 1β-Hydroxylated Vitamin D 3 Analogs Biological Activity and Conformational Analysis of 1β,25-Dihydroxyvitamin D 3 and its Analogues Topological Mimics of the 6-s-cis-Conformer of 1a,25-Dihydroxyvitamin D 3 Based on the Provitamin D Skeleton Chemistry and Biology of Highly Active 22-oxy Analogs of 20-epi Calcitriol with Very Low Binding Affinity to the Vitamin D Recepto New Discoveries in Vitamin D Related Compounds Modelling of Previtamin D Photosynthesis in View of its Conformational Flexibility Active Vitamin D Analogs with Side Chain Hydroxyl Group Occupying Diverse Spatial Region Synthesis and Biological Activity of 23-oxa Vitamin D Analogues Synthesis and Biological Activity of 20-Hydroxylated Vitamin D Analogues 20-Methyl Vitamin D Analogues 2β-Substituted Calcitriols and Other A-Ring Substituted Analogues - Synthesis and Biological Results Syntheses and Biological Activity of 1ß-Substituted Active Vitamin D 3 Analogs Vitamin D Binding Protein Probing the Vitamin D-Sterol Binding Domain of Human Vitamin D-Binding Protein: Chemical Modification of Specific Amino Acid Residues Crystallization and Preliminary X-Ray Investigation of Vitamin D-Binding Protein from Human Serum Effects of Vitamin D-Binding Proteins on Biological Functions of 1 a,25-Dihydroxyvitamin D 3 Analogues Vitamin D Hydroxylases: Biochemistry and Regulation Differences of the Regulation of 24-Hydroxylase Gene Expression in the Kidney and Intestine Regulation of the Ferredoxin Component of Renal Hydroxylases at the Transcriptional and Postradiational Level and of the Protein Inhibitor of Cyclic AMP-Dependent Kinase Site and Rate of Hydroxylation of 1a-OH-D 3 Analogs by CYP27 Not Altered by Increasing Length or Changing Orientation of Vitamin D 3 Side Chain Protein Kinase C Up-Regulates 1 a,25-Dihydroxyvitamin D 3 -Induced Expression of 24-Hydroxylase Gene IGF-I Restores the Age-Related Defect in Renal 1,25(OH) 2 D 3 Biosynthesis in Response to Dietary Phosphorus Restriction in Rats In Vitro Production of 1,25-Dihydroxyvitamin D 3 by Cultured Mouse Kidney Cells and its Regulation by Extracellular Phosphate and IGF-1 The Cytochromes P450 Catalyzing 25-Hydroxylation of Vitamin D and la-Hydroxy lation of 25-Hydroxyvitamin D 3 in Pig Liver Evidence that 1a - and 27-Hydroxylation of 25-Hydroxyvitamin D 3 are Catalyzed by CYP27 in Pig Kidney Mitochondria The Kinetics of Monocyte la-Hydroxy läse in Uremia. Modulation by Calcitriol and 25(OH)D 3 Therapy Eicosanoid Inhibitor and Cytokine Regulation of 1,25(OH) 2 D 3 Synthesis in Synovial Fluid Macrophages from Patients with Inflammatory Arthritis 25-Hydroxyvitamin D-la-Hydroxy läse is Responsible for the Synthesis of 1.25-Dihydroxyvitamin D 3 by Peritoneal Macrophages of CAPD Treated Uremic Patients Influence of Extracellular Calcium in the Kinetic Behaviour of 1-Hydroxylase (1-OHase) and 24-Hydroxylase (24-OHase) in Walker Carcinosarcoma 256 Cells (WS) and in the Renal Proximal Tube Phenotype Cells (LLC-PK1) Insulin and Calcitonin Decrease the Expression of the Renal 25(OH)D-24- Hydroxylase Cytochrome P450 in Diabetic Rats Continuous Activation of 25-Hydroxyvitamin D 3 -24-Hydroxylase mRNA Expression by 1a,25-Dihydroxyvitamin D 3 -3ß-Bromoacetate Regulation of 24-Hydroxylase mRNA Expression by 1a,25(OH) 2 D 3 and its Fluorinated Analogues Comparative Effects of 1,25-Dihydroxyvitamin D 3 and EB 1089 on Murine 25-Hydroxyvitamin D 3 -24-Hydroxylase Vitamin D Metabolism and Catabolism Target Cell Metabolism of Vitamin D and its Analogs In Vivo Regulation of Rat Intestinal 24-Hydroxylase (I-24-OHase): Potential New Role of Calcitonin Metabolism of 1a,25-Dihydroxyvitamin D 3 and One of its A-Ring Diastereomer 1a,25-Dihydroxy-3-Epivitamin D 3 in Neonatal Human Keratinocytes Vitamin D Metabolism in Human Colon Adenocarcinoma-Derived Caco-2 Cells Studies on Vitamin D Metabolism by a Human Small Cell Lung Cancer (SCLC) Cell Line, NCI-H82 The In Vitro Metabolism of Calcipotriol, 1,24(OH) 2 D 3 and 1,25(OH) 2 D 3 Regulation of Tissue Inhibitor of Metalloproteinases (TIMP) by 1,25- and 24,25- Dihydroxyvitamin D 3 in the Rat Growth Plate The Effect of Parathyroid Hormone on Renal 24-Hydroxylase Activity in the Isolated Perfused Rat Kidney Steroidal Hormones as Modulators of Vitamin D Metabolism in Human Keratinocytes Potentialisation of Vitamin D (Analogs) by Cytochrome P-450 Enzyme Inhibitors is Analog- and Cell-type Specific Novel Cleavage of Vitamin D 2 Side Chain During Catabolism by Keratinocyte Cell Line 22-Oxacalcitriol is Metabolized to C 21 Side-Chain-Cleaved Products in Both Liver and Target Cells Metabolism of the 1a,25(OH) 2 D 3 Analog 1a,25(OH) 2 -16-ene-23-yne-D 3 in BALB/c Leukemic Mice and WEHI-3 Myeloid Leukemia Cells Microtubules Mediate Cellular 25(OH)D 3 Traffic and the Response to 1,25(OH) 2 D 3 in Human Monocytes Study of the Metabolism of 1,25-Dihydroxy-16-ene-Vitamin D 3 in Rat Kidney Using On-line HPLC-Electrospray Tandem Mass Spectrometry Human Placental Explants: An Efficient In Vitro Model for Comparative Metabolism of 1,25(OH) 2 D 3 and its Synthetic Analogs 24,25(OH) 2 D 3 Modulates 1,25(OH) 2 D 3 Metabolism in Human Osteoblasts Metabolism of 25 Hydroxy Vitamin D 3 : Kinetics of 23 and 24 Hydroxylases in Human Term Placenta Comparative Study in Vitamin D Metabolism from the View-Point of Ontogeny and Phylogeny Receptors for 1a,25(OH) 2 D 3 Receptor Mediated Genomic Actions of 1,25(OH) 2 D 3 : Modulation by Phosphorylation Modulation of Vitamin D 3 Target Gene Selectivity by Receptor Dimerization The Molecular Basis for the Genomic Actions of the Vitamin D 3 Hormone Expression of RXRa in Human Leukemic Cells During Differentiation Induced by All-Trans Retinoic Acid and 1a,25-Dihydroxyvitamin D Differential Activation of the Vitamin D Receptor (VDR) by 1,25(OH)2- Vitamin D 3 and its 20-Epimers Dopamine Activates Vitamin D Receptor But Not Retinoid Receptor Mediated Transcription Ordered Binding of Human Vitamin D and Retinoid-X Receptor Complexes to Asymmetric Vitamin D-Responsive Elements Immunohistochemical Localization of 1,25-Dihydroxy vitamin D 3 [1,25(OH) 2 D 3 ] Receptors (VDR) in Human and Rat Pancreas Structure-Function Relationship of Human Parathyroid Hormone on Vitamin D Receptor Regulation in Osteoblast-Like Cells (ROS 17/2.8) Insulin-Like Growth Factor I Up-Regulates Intestinal 1,25(OH) 2 D 3 Receptor in Phosphorus Restricted Rats A Peptide C-Terminal to the Second Zn-Finger of Human Vitamin D Receptor is Able to Specify Nuclear Localization Molecular Cloning and Sequencing of a Novel cDNA Related to the Steroid/Thyroid/Vitamin Family of Nuclear Receptors from a Vitamin DDeficient Chick Intestinal cDNA Library Isolation and Analysis of cDNA Encoding a Naturally-Occurring Truncated Form of the Human Vitamin D Receptor EB 1089, a Vitamin D Analogue, Induces the Vitamin D Receptor to Form Selective Receptor Complexes Depending on Cell Type Gene Regulation 1,25(OH) 2 D 3 Response Elements: Is There an Order? Vitamin D Regulation of Osteocalcin Gene Transcription: A Model for Defining Molecular Mechanisms of 1,25(OH) 2 D 3 Control of Osteoblast Growth and Differentiation Regulation of Integrin Expression by 1,25 Dihydroxyvitamin D 3 Identification of a Chicken Intestinal DNA Binding Activity Not Related to the Vitamin D Receptor, but Capable of Specific Binding to Vitamin D Response Elements Transcriptional Regulation of the Avian Mitochondrial Genome by Altered Dietary Vitamin D 3 Status: A Comparison of Intestinal and Kidney Responses A Novel Vitamin D Response Element in the Murine c-fos Promoter 1,25(OH) 2 -Vitamin D3 (D3) Interactions with 3,5,3'-Triiodothyronine (T3) Signaling in 3 Osteosarcoma Cell Lines 1,25(OH) 2 -Vitamin D 3 (D 3 ) Signaling in HT-29 Cells: Interactions with 9-eis Retinoic Acid (9-eis RA) Protein Inhibitor of Cyclic AMP-Dependent Protein Kinase: Genomic Cloning of a 1,25(OH) 2 D 3 Down-Regulated Protein Lack of 9-eis Retinoic Acid Effect on Renal 24-Hydroxylase mRNA Expression by 1,25-Dihydroxyvitamin D 3 In Vivo Regulation of Osteopontin Expression by Calcitriol in Mouse Epidermal JB6 Cells Dissociation between Regulation of Growth and C-myc Oncogen Expression by Vitamin D in Caco-2 Cells TGF-ßl Inhibits the Induction of Osteocalcin Gene by 1,25(OH) 2 D 3 at the Level of Transcription Mechanism of Action of 1,25-Dihydroxyvitamin D Differs in Kidney, Intestine, and Bone Cell Lines mRNA Levels of the Inhibitor Protein of cAMP-Dependent Protein Kinase are Regulated by 1,25(OH) 2 D 3 and Forskolin Vitamin D Receptor (VDR) Interactions with Vitamin D 3 Response Elements (VDRE) in the Parathyroid Hormone (PTH) and Osteocalcin Genes are Different Coordinate Regulation of Rat Parathyroid Gland Function by Calcium and 1,25- Dihydroxyvitamin D 3 Phosphorylation Pathways Affect Binding of AP-1 and Vitamin D Receptor to their Combined Response Element in the Promoter Region of Human Osteocalcin Gene Rapid Actions of Vitamin D Steroids Transmembrane Signal Pathways Induced by Calcitriol, Estradiol, Testosterone and Progesterone in Osteoblasts Non-Nuclear Actions of 1a,25(OH) 2 D 3 and 24R,25(OH) 2 D 3 in Mediating Intestinal Calcium Transport: The Use of Analogs to Study Membrane Receptors for Vitamin D Metabolites and to Determine Receptor Ligand Conformational Preferences Nongenomic Effects of Vitamin D Binding of the Occupied Vitamin D Receptor (VDR) to Extra-Nuclear Sites: A Potential Mechanism of Nongenomic Actions of 1a,25(OH) 2 D 3 A Common Mechanism for the Vitamin D Reeeptor Activation and for the Nongenomic Actions of Calcitriol The Calciotropic Hormone 1,25(OH) 2 -Vitamin D 3 Stimulates Phospholipase D Activity in Cultured Muscle Cells Rapid Non-Genomic Effect of 1a,25-Dihydroxyvitamin D 3 on Osteoblast Nuclei 1a,25-Dìhydroxyvitamin D 3 Induces a Rapid and Sustained Increase in Cytosolic Calcium in Cultured Human Keratinocytes Aged-Related Changes in the Non-Genomic Response of Intestinal Mammalian Cells to 1,25-Dihydroxy-Vitamin D 3 Video Imaging of Intracellular Calcium in Insulinoma Cells: Effects of 1,25(OH) 2 D 3 Cellular Signalling Responses Mediated by 1,25(OH) 2 -Vitamin D 3 in Rat and Chick Myoblasts Involvement of Adenylate Cyclase System in 1,25-Dihydroxyvitamin D 3 Rapid Stimulation of Ca 2 + Uptake by Heart Cells Specific Binding of 1,25-Dihydroxyvitamin D 3 to Rat Colonocyte Basolateral Membranes Protein Kinase C Participates in the Signal Transduction Pathway Triggered by 1,25-Dihydroxyvitamin D 3 in Myocytes Calbindins D—Function and Gene Regulation: Calcium Transport Mechanistic Studies on Intestinal Ca 2 + Transport Vitamin D, the Intestinal Plasma Membrane Calcium Pump Gene Expression and the Calbindins Tissue Specific Calbindin-D 9K Gene Regulation by Calcitriol and Sexual Hormones Proteins that Bind to the Calbindin-D 9K Promoter: Known Factors and a New Intestinal Factor Studies of the Human Calbindin-D 9K Gene Calbindins Revisited in the Rat Dental Pulp In Situ Hybridization of Calbindins mRNAs in Rat Ameloblasts Immunoreactive Calbindins-D 28K and 9K Mineralization of Rat Epiphyseal Chondrocytes in Culture Regulation of Calbindin-D 28K by Parathyroid Hormone in MDBK Cells Phosphorylation and Modulation of Calbindin D 28K by Activation of Protein Kinase C (PKC) Caco-2 Cells: A Human Intestinal Cell Line for Studying the Biologic Activity of Vitamin D Analogs EGF Down Regulates Both Calbindin D 28K and the VDR in MDBK Cells Does Calbindin-D 28K Buffer Intracellular Free Calcium? Calbindin-D 28K (CaBP-D 28K ) in the Rat Endocrine Pancreas: In Vivo and In Vitro Immunolocalization and its Regulation by Vitamin D 3 Deficiency and 1,25- Dihydroxyvitamin D 3 Effect of Two Antiestrogens (Tamoxifen and ICI 182780) on Calbindin-D 9K Gene Expression In Vivo in the Rat Uterus, and In Vitro in Primary Cultures of Myometrial Cells Identification of a 9 kDa Calcium-Binding Protein in the Chick as Calbindin-D 9K Effect of Antisense Sequences Against Calretinin on WiDr Cells Intestinal Absorption of Calcium and Strontium Demonstrate a Similar Response to Calcitriol Treatment Physiological Concentrations of 24,25(OH) 2 Vitamin D 3 Decrease the Intestinal Calcium Uptake in the Atlantic Cod, Gadus Morhua Effects of Vitamin D and DL-Buthionine-S, R-Sulfoximine on Intestinal Calcium Absorption 1,25-(OH) 2 D 3 Stimulates Ca 2+ -Uptake Across the Duodenal Brush Border by at Least Two Independent Mechanisms Effect of Heavy Metals on the Level of Calbindin D 28K and the Assimilation of Ca in Chick Duodenum Apparent Nephron Localization of the 1,25(OH) 2 D 3 -Stimulated Calmodulin Binding Proteins in the Rat Kidney Raised Intestinal Calcium Secretion in the Young Oophorectomised Rat Validation of a Simple Test Measuring Intestinal Calcium Absorption Using Strontium as a Marker Cell Differentiation In Vitro Effects of Potent Vitamin D 3 Analogs on Proliferation and Differentiation of Seven Human Breast Cancer Cell Lines Terminal Differentiation of Human Leukemia Cells (HL60) by a Combination of 1,25-Dihydroxyvitamin D 3 and Retinoic Acid (All Trans or 9-Cis) 1,25-Dihydroxyvitamin D 3 Induces Growth of Thyroid C Cells and Inhibits Calcitonin Secretion In Vitro Differentiation of Human Myelomonocytic Leukemia Cell Lines by Retinoic Acid and Vitamin D 3 Analogs, MC903 and EB1089: Characterization of Cooperative Effects Effect of Ascorbate and Calcitriol on HL-60 Promyelocytic Cell Line Proliferation and Differentiation Evidence for a Vitamin D Paracrine System Regulating Fetal Pneumocyte Type II Maturation: Local Synthesis of 1,25-(OH) 2 D 3 by Lung Fibroblasts Inhibition of IEC-6 Cell Growth by 1,25(OH) 2 D 3 : Involvement of TGFß Interactions between Vitamin D Derivatives, Retinoids and Granulocyte Macrophage - Colony Stimulating Factor in Leukemic Cell Differentiation 1,25(OH) 2 D 3 and Agents that Increase Intracellular cAMP Synergistically Inhibit the Proliferation of Mouse Fibroblasts 1a,25-Dihydroxyvitamin D Rapidly Triggers Inhibition of Fibroblast Contraction of Collagen Lattices Cancer Immunology Dermatology Neurosciences Renal Osteodystrophy Bone and Cartilage Miscellaneous Biological Actions of Vitamin D Metabolites and Analogs Assays for Vitamin D Steroids Nutrition Osteoporosis Neonatology and Pregnancy Gerontology Other Basic Science Topics Other Clinical Topics Author Index Subject Index Cell Line Index Zoo Index