Organ-Selective Actions of Steroid Hormones PDF
Preview Organ-Selective Actions of Steroid Hormones
Ernst Schering Research Foundation Workshop 16 Organ-Selective Actions of Steroid Hormones Springer-Verlag Berlin Heidelberg GmbH Ernst Schering Research Foundation Workshop 16 Organ-Selective Actions of Steroid Hormones D. T. Baird, G. SchOtz, R. Krattenmacher Editors With 44 Figures and 8 Tables Springer ISBN 978-3-662-09155-5 Die Deutsche Bibliothek - CIP-Einheitsaufnahme Ernst -Schering-Forschungsgesellschaft <Berlin>: Ernst Schering Research Foundation workshop. Friiher Schriftenreihe. - Friiher angezeigt u.d.T.: Ernst-Schering-Forschungsgesellschaft <Berlin>: Schering Foundation workshop. - Teilw. u.d.T.: Ernst-Schering-Forschungs gesellschaft <Berlin>: Schering Foundation workshop ISSN 0947-6075 NE: Ernst-Schering-Forschungsgesellschaft <Berlin>; Schering Foundation workshop; HST 16. Organ selective actions of steroid hormones. - 1995 Organ selective actions of steroid hormones / D.T. Baird ... ed. (Ernst Schering Research Foundation workshop; 16) ISBN 978-3-662-09155-5 ISBN 978-3-662-09153-1 (eBook) DOI 10.1007/978-3-662-09153-1 NE: Baird, David T. [Hrsg.J CIP data applied for This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illus trations, recitation, broadcasting, reproduction on microfilms or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag Berlin Heidelberg GmbH. Viol-ations are liable for prosecution under the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1995 Originally published by Springer-Verlag Berlin Heidelberg New York in 1995 Softcover reprint of the hardcover 1st edition 1995 The use of general descriptive names, registered names, trademarks, etc. in this publica tion does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Typesetting: Data conversion by Springer-Verlag 21/3135-5432 1 0 - Printed on acid-free paper Preface Pharmacodynamics can be defined as the study of the biochemical and physiological effects of drugs and mechanisms of their action. The lat ter aspect of the subject is perhaps the most fundamental challenge to the investigator in pharmacology, and information derived from such studies is useful for the clinician. The objectives of the analysis of drug action are to identify the primary action, to delineate the chemical or physical interactions between drug and cell and to characterize the full sequence and scope of actions and effects. Such a complete analysis provides the basis for both the rational therapeutic use of a drug and the design of new therapeutic agents. The last decade has witnessed a vast extension and coalescence of our knowledge of the structures, mechanism of action, and biochemical functions of steroid hormone receptors. Steroid receptors and many other proteins that are involved in biological signal transduction have been purified. Molecular cloning has provided amino acid sequences for steroid hormone receptors, permitted their expression and study in genetically defined backgrounds and allowed a detailed analysis of structure-function relationships of signaling molecules through site-di rected mutagenesis. Due to the specific expression of steroid hormone receptors in dif ferent target tissues, organ-specific action is not a new feature of ste roids. However, the rapidly increasing knowledge of the complex set of intracellular interactions opens numerous further options for organ specificity. For example, in epithelial cells of the distal nephron, aldos terone can occupy its receptor exclusively only when the enzyme I I ~HSD, which is colocalized with the mineralocorticoid receptor, lo cally inactivates glucocorticoids. VI Preface Fig. 1. The participants of the workshop. From left to right, background: R. L. Sutherland, R. T. Turner, D. T. Baird, G. Schlitz, M. Bygdeman; foreground: J. S. Finkelstein, D. P. McDonnell, B. S. Katzenellenbogen, H. F. DeLuca, M. C. Farach-Carson, R. Krattenmacher It would necessarily be beyond the scope of this workshop to sum marize all aspects of organ-specific actions of steroid hormones. Our aim was rather to highlight and discuss recent findings concerning basic molecular mechanisms of organ specificity and to bring them into close relationship with clinical aspects. The contributions of the Preface VII leading experts in steroid physiology who participated in this work shop from May 17-19, 1995 will lead to a better understanding of the underlying mechanisms of organ selectivity and help towards im proved therapies by taking advantage of tissue specificity. The editors gratefully acknowledge the contributions of the authors of the chapters in this book and the assistance provided by the Ernst Schering Research Foundation, in particular by Dr. V.F. Habenicht and Mrs V. Wanke. D.T. Baird G. Schutz R. Krattenmacher Table of Contents 1 Development of Tissue-Selective Estrogen Receptor Modulators D. P. McDonnell, B. A. Lieberman, and 1. Norris . . 2 Estrogen-Receptor and Antiestrogen-Receptor Complexes: Cell-and Promoter-Specific Effects and Interactions with Second Messenger Signaling Pathways B. S. Katzenellenbogen, M. M. Montano, W. L. Kraus, S. M. Aronica, N. Fujimoto, and P. LeGoff ... . . . 29 3 Analysis of Genetically Altered Mice Without Glucocorticoid Receptor W. Schmid, T. Cole, 1. Blendy, L. Montoliu, and G. Schiltz 51 4 Organ-Selective Actions of Tamoxifen and Other Partial Antiestrogens R. T. Turner . ............. . 65 5 Progestin Regulation of Cell Proliferation in the Breast and Endometrium R. L. Sutherland, C. S. L. Lee, A. L. Cornish, and E. A. Musgrove 85 6 Central Versus Endometrial Effects of Antiprogestins: Is Endometrial Selectivity Possible? M. Bygdeman, K. Gemzell-Danielsson, and M. L. Swahn .. 107 X Table of Contents 7 Androgen Action on the Bone 1. S. Finkelstein . . . . . . . . . . . . . . . . . . . . . . .. 121 8 General Principles of Vitamin D Action and Mechanism-Based Search for Analogs with Specific Actions H. F. DeLuca, C. Zierold, and H. M. Darwish ....... 137 9 Organ-Specific Actions of Vitamin D Analogs: Relevance of Rapid Effects M. C. Farach-Carson and S. E. Guggino .......... 161 Subject Index ......................................... 181 Previous Volumes Published in this Series .................. 183 List of Editors and Contributors Editors D. T. Baird Department of Obstetrics and Gynaecology, Centre for Reproductive Biology, University of Edinburgh, 37 Chalmers Street, Edinburgh EH3 9EW, Scotland G. Schutz German Cancer Research Center, Molecular Biology of the Cell I, 1m Neuenheimer Feld 280, 69120 Heidelberg, Germany R. Krattenmacher Research Laboratories of Schering AG, 13342 Berlin, Germany Contributors S. M. Aronica Department of Physiology and Biophysics, University of Illinois and University of Illinois College of Medicine, 524 Burrill Hall, 407 South Goodwin Avenue, Urbana, IL 61801-3704, USA J. Blendy German Cancer Research Center, Molecular Biology of the Cell I, 1m Neuenheimer Feld 280, 69120 Heidelberg, Germany M. Bygdeman Department of Woman and Child Health, Division for Obstetrics and Gynecology, Karolinska Hospital, 17176 Stockholm, Sweden
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