Vitamin D. Chemical, Biochemical and Clinical Update: Proceedings of the Sixth Workshop on Vitamin D Merano, Italy, March 1985 [Reprint 2020 ed.] 9783112330005, 9783112329993

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Vitamin D Chemical, Biochemical and Clinical Update

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Vitamin D Chemical, Biochemical and Clinical Update Proceedings of the Sixth Workshop on Vitamin D Merano, Italy, March 1985 Editors A. W Norman • K Schaefer H.-G. Grigoleit • D. v. Herrath

W G DE

Walter de Gruyter • Berlin • New York 1985

Editors A. W Norman, Professor Ph. D. Department of Biochemistry University of California Riverside, CA 92521 USA

H.-G. Grigoleit, Dr. Klinische Pharmakologie Hoechst A G D-6230 Frankfurt 80 Federal Republic of Germany

K. Schaefer, Professor, Dr. St. Joseph-Krankenhaus I D-1000 Berün 42 Federal Republic of Germany

D. von Herrath, Dr. St. Joseph-Krankenhaus I 1000 Berlin 42 Federal Republic of Germany

'Library of Congress Cataloging in Publication Data Workshop on Vitamin D (6th : 1985 : Merano, Italy) Vitamin D : chemical, biological, and clinical update. Includes bibliographies and indexes. 1. Vitamin D~Congresses. 2. Vitamin D~Metabolism~Congresses. 3. Vitamin D~Therapeutic use-Congresses. I. Norman, A. W (Anthony W), 1938. II. Title. [DNLM: 1. Vitamin D-congresses. W3 W0512C 6th 1985 v / QU 173 W926 1985v] QP772.V53W67 1985 612'.399 85-10403 ISBN 0-89925-066-1 (U.S.)

CIP-Kurztitelaufnahme der Deutschen Bibliothek Vitamin D : proceedings of the ... Workshop on Vitamin D. Berlin ; New York : de Gruyter Früher u. d. T.: Vitamin D and problems related to uremic bone disease NE: Workshop on Vitamin D 6. Chemical, biochemical and clinical update : Merano, Italy, March 1985. - 1985. ISBN 3-11-010181-5 (Berlin) ISBN 0-89925-066-1 (New York)

ISBN 3 110101815 Walter de Gruyter • Berlin • New York ISBN 0-89925-066-1 Walter de Gruyter, Inc., New York Copyright © 1985 by Walter de Gruyter & Co., Berlin 30 All rights reserved, including those of translation into foreign languages. No part ofthis book may be reproduced in any form - by photoprint, microfilm or any other means nor transmitted nor translated into a machine language without written permission from the publisher. Printing: Gerike GmbH, Berlin. Binding: Dieter Mikolai, Berlin. Printed in Germany.

Foreword The Sixth Workshop on Vitamin D was held in the Centro Congressi of Merano, Italy, which is located in the northern Tyrol region of that country. The meeting was held from March 17-22,1985. In attendance were 474 registered delegates from 27 countries. These include representatives from Algeria (2), Argentina (1), Australia (14), Austria (5), Belgium (12), Canada (15), Denmark (20), Federal Republic ofGermany (24), Finland (6), France (37), German Democratic Republic (17, India (1), Israel (17), Italy (33), Japan (36), Norway (9), Poland (4), Saudi Arabia (2), South Afrika (2), Spain (7), Sweden (13), Switzerland (13), The Netherlands (25), Turkey (3), United Kingdom (36), United States (133) and Yugoslavia (2). Interest and attendance at Vitamin D Workshops still continues to grow. Tabulated below are the dates and attendance as well as number oftalks given at the six Vitamin D Workshops that have now been held. Since the time of the Fifth Workshop held in Williamsburg, Virginia in February of1982, there has been a clear increase in attendance at the Workshop as well as in the number of submitted presentations. This reflects the continuing growth in research frontiers related to the vitamin D endocrine system.

Workshop Number

Date

I

October 1973 October 1974 January 1977 February 1979 February 1982 March 1985

II III IV V VI

Number of Delegates

Number of Countries Represented

Number of Presentations Talks Posters

Presentations per Delegate

56

3

5

—

0.09

221

22

84

—

0.39

332

20

45

124

0.51

402

26

80

205

0.76

455

25

95

298

0.86

474

27

77

380

0.96

The formal program of the Sixth Workshop on Vitamin D included 48 verbal presentations by invited speakers and 29 promoted free communications as well as 380 poster presentations. This program was conceived and put together by the Program Committee of the Sixth Workshop; members of this committee included R. Bouillon (Belgium), A. Caniggia (Italy), J. W Coburn (USA), H. F DeLuca (USA), S. Edelstein (Israel), J. A. Eisman (Australia), M. R. Haussler (USA), M. F Holick

VI (USA), J. A. Kanis (United Kingdom), D. E. M. Lawson (United Kingdom), A. W Norman (USA), J. L. H. O'Riordan (United Kingdom), W H. Okamura (USA), B. L. Riggs (USA), T. Suda (Japan), M. Thomasset (France), M. Uskokovic (USA), R. H. Wasserman (USA). A major responsibility ofthe Program Committee was to review the 409 abstracts submitted as Free Communications and to individually „score" each abstract; from this group, 29 abstracts were selected by the Program Committee for inclusion on the verbal program ofthe meeting. In addition a special feature of the Sixth Workshop was a new component of the program entitled, „Late Breaking Events." A sub-committee of the Program Committee evaluated abstracts which were turned in at the time of the meeting in Merano; these presentations were to cover laboratory developments which occurred since the time of submission of abstracts in October 1984 and the occurrence of the meeting in March 1985. A total of 8 abstracts were received and 6 were programmed on the last day of the meeting as 7-minute presentations; the chapters for each of these „Late Breaking Events" are included in this volume. Presented in this volume are papers prepared by the invited speakers as well as submitters ofmany ofthe Free Communications. The chapters in this book are grouped according to their general subject matter based on the classification made by the submitting authors, e. g. vitamin D chemistry, vitamin D metabolism and catabolism, receptors for l,25(OH)2D3, renal osteodystrophy, osteoporosis, etc. Due to the large number of Free Communications (380) a major effort was made to allow adequate time for presentation and discussion of the many significant results that were presented by this mechanism. There were seven Poster Sessions scheduled throughout the meeting; during a 2-3 hour time interval the posters were „manned" by the submitting authors. Importantly, however, each poster was available for review for a minimum of 10-11 hours each day. Thus on each day approximately 100 posters were continuously presented throughout the day. The highlights of the Sixth Workshop on Vitamin D were again amazing in terms of ther variety; undoubtedly this reflects the diverse interests of the chemists, biochemists, physiologists and clinicians who attended the meeting and who are actively conducting research in the various aspects of the vitamin D endocrine system. Clinical highlights included presentation of results of ongoing trials of l,25(OH) 2 D 3 in the treatment of post-menopausal osteoporosis. There was uniformity of agreement in the four osteoporosis presentations that under appropriate circumstances l,25(OH)2D3 may make an important contribution to available treatment modalities. Also there was continuing status reports on the effectiveness of 1,25(0 H) 2 D 3 in treatment of renal osteodystrophy. Several presentations focused on the application of l,25(OH)2D3 in the early onset of renal failure; again the utility of l,25(OH)2D3 was supported by the presentations given at the Workshop.

VII Several significant advances were also reported in terms of our basic understanding of the vitamin D endocrine system. Notable in this regard was the presentation ofthe molecular biological cloning of the mRNA for the D-binding protein; this resulted in the generation of the primary amino acid sequence for both the rat as well as human DBP This important D-transport protein is apparently related to the protein families of albumin and a-feto protein. Also the amino acid sequence was reported, as derived from classical sequencing techniques, of the principle intestinal vitamin D induced 28,000 dalton calcium binding protein. An intriguing chemical observation was the sythesis of an analog of l,25(OH) 2 D 3 , namely l,25S,26(OH) 3 -A22-D 3 which was highly active in mediating cell differentiation but had a diminished activity in terms of its hypercalcemic actions as compared to the parent l,25(OH) 2 D 3 . Clear and incisive evidence was presented that l,25(OH) 2 D 3 could be produced at various extra-renal sites; in this regard it was intriguing to learn that y-interferon could stimulate the production of l,25(OH) 2 D 3 by pulmonary macrophages. Certainly the area of the program which attracted the largest submission of Free Communications was that relating to l,25(OH) 2 D 3 receptors and their participation in cell differentiation. It is clear from these collective results that a micro/paracrine endocrine system exists for l,25(OH) 2 D 3 in terms ofmediating appropriate stem cell differentiation. The Advisory Committee and the Program Committee would like to acknowledge the financial support of American Bio-Science Laboratories, Amersham International, Chugai Pharmaceutical Co. Ltd., Du Pont NEN Products Division, E. Merck, Fondazione Hoechst, Gambro Dialysatoren, Hoffmann-La Roche and Co. Ltd. (Basle), Hoffmann-La Roche (Nutley), Immuno Nuclear, Leo Pharmaceutical Products, Mead Johnson Nutritional Division, Nuclear Data, Inc., Roche S. P A., Roussel Maestretti, Teijin Limited, and The Procter and Gamble Company. Without this generous governmental and multi-corporate financial support it would have been impossible to have a Vitamin D Workshop which included such a comprehensive program and world-wide attendance. A special tribute is also due to the tireless efforts of the Workshop Conference Secretaries. Ms. Lean S. Gill and her colleagues in Riverside, Ms. June E. Bishop and Ms. Ann Hall were responsible for the bulk of the secretarial activities related to production of the abstract book and the advanced registration process. In addition Workshop Secretary, Ms. Pam Moore effectively and professionally handled the multitude of details concerned with the actual conduct of the meeting in Merano; in this capacity she was ably assisted by both Ms. June Bishop and Ms. Tieneka Hansson. Anthony W Norman, Riverside Klaus Schaefer, Berlin Dietrich von Herrath, Berlin Hans-Giinther Grigoleit, Frankfurt

March 1985

OFFICIAL SPONSORS S I X T H W O R K S H O P ON VITAMIN D

American B i o - S c i e n c e USA

Laboratories

Amersham International England

pic

C h u g a i P h a r m a c e u t i c a l Co L t d Japan Du Pont N E N P r o d u c t s USA E Merck F e d R e p of Fondazione Italy

Division

Germany Hoechst

Gambro Dialysatoren F e d Rep G e r m a n y

(Munich)

H o f f m a n n - L a R o c h e & Co L t d Switzerland Hoffman-La Roche USA Immuno USA

(Nutley, New

Nuclear

Leo Pharmaceutical Denmark

Products

M e a d Johnson Nutritional USA N u c l e a r D a t a , Inc (Molsgaard Medical Roche Italy Roussel Italy

(Basle)

Division

A/S)

S.P.A.

Maestretti

Teijin Limited Japan The Procter & Gamble USA

Company

Jersey)

Contents Vitamin D Metabolism and Catabolism A Comparison of Vitamin D2 and D3 in Man* L. Tjellesen, C. Christiansen, L. Hummer

3

Metabolism of 24R,25-Dihydroxyvitamin D 3 : An Approach from Synthetic Study* S. Yamada, E. Ino, H. Takayama, T. Suda

13

Extra-Renal Production of l,25(OH)2D3: The Metabolism of Vitamin D by Non-Traditional Tissues* R. S. Mason

23

Regulation of Pre-Proparathyroid Hormone mRNA in Bovine Parathyroid Cells in Culture by Vitamin D Metabolites J. Silver, J. Russell, L. M. Sherwood

33

Metabolism of Vitamin D in Pigs with Pseudo Vitamin D Deficiency Rickets after Treatment with high Doses of Vitamin D3 R. Kaune, J. Harmeyer

35

Isolation and Identification of 25-Hydroxydihydrotachysterol, 1 a, 25-Dihydroxydihydrotachysterol and lß,25-Dihydroxydihydrotachysterol 37 R. Bosch, C. Versluis, J. K. Terluow, J. H. H. Thijssen, S. A. Duursma Stress Testing of Calcium Regulatory Hormones Using Outpatient Dietary Calcium Deprivation R. L. Prince, B. G. Hutchison, R. W Retallack, J. C. Kent, G. N. Kent

39

Vitamin D Metabolism and Glucocorticoid Treatment S. Adami, R. Dorizzi, D. Tartarotti, B. Imbimbo, V Lo Cascio

41

Vitamin D-Dependent Rickets Type I in Pigs J. Fox, E. M. W Maunder, A. D. Care, V A. Randall

43

Metabolism of 25-OH-D3 in Human Promyelocytic Leukemia Cells (HI^60). Isolation and Identification of 19-Nor-10-Keto-25-C)H-D3 S. Ishizuka, T. Matsui, Y. Nakao, T. Fujita, T. Okabe, A. W Norman 45 Influence of Caffeine on the Metabolism of Calcium and Vitamin D in Young and Adult Rats J . K Yeh, J.EAloia * Invited Presentation

47

X Pharmacokinetics of 1,25-Dihydroxyvitamin D in the Rat M. J. Jongen, J. E. Bishop, C. Cade, A. W Norman

49

Effect of a Retinoid on Ca and Vitamin D Metabolism in Thyroparathyroidectomized (TPTX) Rats U. Trechsel, H. Fleisch

51

Fatty Acid Esters of Calciol and Ercalciol in Humans and their possible Metabolic Function B. Zagalak, E Neuheiser, H-Ch. Curtius

53

Detection of 1,24,25-Trihydroxyvitamin D 3 in Solanum Malacoxylon Leaf Extracts with Ruminal Fluid R. L. Boland, M. I. Skliar, A. W Norman

55

The Pathogenesis of Hypercalcaemia in Vitamin D Poisoning M. Davies, E. B. Mawer

57

Vitamin D 3 Uptake by Isolated Perfused Liver is dependent on its Transport by Lipoproteins and is a Surface Phenomenon J. Silver, E. Ziv

59

Effects of Lipopolysaccharides on Conversion of 25-Hydroxyvitamin D 3 by Normal Human Polysaccharides H. Reichel, H. P Koeffler, J. E. Bishop, A. W Norman

61

Control of 1-Hydroxylase Activity in Primary Hyperparathyroid Patients V Lo Cascio, S. Adami, R. Dorizzi, D. Tartarotti, G. Salvagno

63

I,25-Dihydroxy-Vitamin D in Serum after Oral Administration of Vitamin D 3 in Healthy Subjects S. Issa, B. Emde, H. V Lilienfeld-Toal, W Bumeister

65

Differences in the Rate of Metabolism of Vitamin D 2 and Vitamin D 3 in Mammals I. Holmberg, T. Berlin, I. Björkhem

67

Metabolism of 1,25-Dihydroxyergocalciferol: Relation to the Biological Differences between Ergocalciferol and Cholecalciferol J. L. Napoli, R. L. Horst

69

Serum l,25(OH) 2 D Levels Increase after oral Administration of Thyrotropin-Releasing Hormone T. L. Storm, G. Thamsborg, S. Ladefoged, B. Lund, O. H. Sorensen

71

Vitamin D Metabolism in Liver Diseases R. Morita, M. Fukunaga, N. Otsuka, T. Sone, S. Dokoh, Y. Fukuda, I. Yamamoto, K. Torizuka

73

XI Vitamin D Metabolism: the Renal-Pituitary Axis* R. W Gray, J. Lemann jr.

75

Receptors for l,25(OH)2D3 Functions and Mechanisms of Action of the 1,25-Dihydroxyvitamin D 3 Receptor* M. R. Haussier, C. A. Donaldson, M. A. Kelly, D. J. Mangelsdorf, S. L. Marion, J. W Pike

83

Ultrastructural-Immunocytochemical Localization of 1,25-DihydroxyVitamin D 3 G. Boivin, P Mesgiuch, G. Morel, J. W Pike, P M. Dubois, P J. Meunier, M. R. Haussler

93

1,25-Dihydroxyvitamin D Receptor and Vitamin D-dependent Calcium - binding Protein in Rat Brain: Comparative Immunocytochemical Localization T. L. Clemens, X. Y. Zhou, J. W Pike, M. R. Haussler, R. S. Sloviter

95

New Insights into Mediators of Vitamin D Action* J. W Pike

97

Resistance to 1,25-Dihydroxyergocalciferol in Man and in Other Species* S. J. Marx, U. A. Liberman, C. Eil, D. A. Degrange, M. M. Bliziotes

107

Administration of 1,25-Dihydroxyvitamin D 3 Results in Increased Choline Acetyltransferase Activity in Specific Brain Nuclei J. Sonnenberg, V N. Luine, L. Krey, S. Christakos

117

Comparison of Cellular and Subcellular Distribution of Vitamin D Metabolites [l,25(OH)2 Vitamin D 3 , 24,25(OH)2 Vitamin D 3 , 25(OH) Vitamin D3] in Target Tissue W E. Stumpf, S. A. Clark, Y S. Kim, H. F De Luca

119

Effect of Vitamin D Deficiency and Supplement on PTH Degradation by the Kidney T. Fujita, H. Baba, M. Fukase, M. Sase, M. Fukushima, Y. Nishii

121

In Vitro Stability of the Calf Thymus 1,25-Dihydroxyvitamin D 3 Receptor T. Koskinen, M. Hahl

123

l,25(OH)2D3 Receptors in Sertoli Cells and Seminiferous Tubules in Mouse and Rat J. Merke, U. Hügel, E. Ritz

125

* Invited Presentation

XII l,25(OH)2D3 Receptor in Pulmonary Alveolar Macrophages J. E. Bishop, H. Reichel, H. E Koeffler, A. W Norman

127

24R,25(OH)2D3: An Allosteric Effector of l,25(OH)2D3 Binding to its Chick Intestinal Receptor E Wilhelm, E E Ross, A. W Norman

129

Effect of Calcium and Phosphate on l,25(OH) 2 D Receptor in Osteogenic Sarcoma Cell Line (UMR106) M. Nakada, M. Fukase, Y. Imai, Y Kinoshita, T. Fujita

131

Temporal relationship of 1,25-Dihydroxycholecalciferol Receptor Expression and Effects on Activated Lymphocytes D. M. Prowedini, C. D. Tsoukas, L. J. Deftos, S. C. Manolagas

133

Is Ligand Overestimation Responsible for the Observed Cooperativity in the Binding of 1,25-Dihydroxyvitamin D 3 to Chick Intestinal Chromatin E E Ross, E E. Wilhelm, A. W Norman

135

Accumulating Evidence for a Physiological Role for 1,25-Dihydroxyvitamin D 3 in New Targets: Testis and Heart M. R. Walters, B. C. Osmundsen, R. M. Carter, E C. Riggle, J. R. Jeter

137

Chemical Synthesis and Biological Evaluation of Photoaffinity - Labelled Derivatives of Vitamin D 3 , and 1,25-Dihydroxyvitamin D 3 M. Ray, S. D. Rose, S. A. Holick, M. E Holick

143

Multiple Forms of Chicken Intestinal Nuclear 1,25-Dihydroxyvitamin D 3 (l,25(OH)2D3) Receptors W S. Mellon, S. Radparvar

145

Defective Binding and Function of 1,25-Dihydroxy Vitamin D 3 (l,25(OH)2D3) Receptors in Peripheral Mononuclear Cells of Patients with End Organ Resistance to l,25(OH) 2 D R Koren, A. Ravid, Z. Hochberg, Y Weisman, A. Novogrodsky, U. A. Liberman

147

Tryptic Cleavage of Chick 1,25-Dihydroxyvitamin D 3 Receptor E. A. Allegretto, J. W Pike

149

Testicular Calcitriol Receptors; Appearance during Development and Presence in Adult Testicular Cell Cultures E O. Levy, L. Eikvar, A. Freysa, J. Cervenka, T. Yoganathan, V Hansson

151

1,25-Dihydroxyvitamin D 3 Receptors and Activities in Skeletal and Heart Muscle R. U. Simpson, G. A. Thomas, A. J. Arnold

153

XIII Impact of Microcomputers on Vitamin D Research* G. Jones

155

Cell Differentiation and Vitamin D (+ Metabolites) 1,25-Dihydroxyvitamin D 3 and the Hematopoetic System* H. Reichel, H. P Koeffler, R. Barbers, R. Munker, A. W Norman

167

Vitamin D and Macrophage Differentiation* S. L. Teitelbaum, Z. Bar-Shavit, E H. Reitsma, H. G. Welgus, A. J. Kahn . . . . 177 Similarity of the Effects of l,25(OH)2D3 and Retinoic Acid on Interleukin (IL) 1, 2 and 3 Production U. Trechsel, V Evequoz, B. Hodler, H. Fleisch

183

Synergistic Regulation of 1,25-Dihydroxyvitamin D 3 and ^-Interferon in Myc Oncogene Expression on Human Promyelocyte, HL-60 T. Matsui, Y. Nakao, T. Nakagawa, T. Koizumi, Y Katakami, T. Sugiyama, T. Fujita 185 Modulation of Cell Differentiation and Tumor Promotion by lff,25-Dihydroxyvitamin D3 [1