Steroid Hormone Action and Cancer

Steroid Hormone Action and Cancer

CURRENT TOPICS IN MOLECULAR ENDOCRINOLOGY Series Editors: Bert W. O'Malley and Anthony R. Means Department of Cell Biology Baylor College of Medicine Houston, Texas Volume 1: Volume 2: Volume 3: Volume 4: Hormone Binding and Target Cell Activation in the Testis Edited by Maria L. Dufau and Anthony R. Means Hormonal Regulation of Spermatogenesis Edited by Frank S. French, Vidar Hansson, E. Martin Ritzen, and Shihadeh N. Nayfeh Hypothalamus and Endocrine Functions Edited by Fernand Labrie, Joseph Meites, and Georges Pelletier Steroid Hormone Action and Cancer Edited by K.M.J. Menon and Jerry R. Reel A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher.

Steroid Hormone Action and Cancer Edited by K. M.l Menon University of Michigan Medical School Ann Arbor, Michigan and Jerry R. Reel Parke Davis Research Laboratories Ann Arbor, Michigan PLENUM PRESS NEW YORK AND LONDON

Main entry under title: Library of Congress Cataloging in Publication Data Steroid hormone action and cancer. (Current topics in molecular endocrinology; v. 4) Based on the proceedings of a conference held at the University of Michigan, Ann Arbor, Oct. 27-29, 1975, and sponsored by the Dept. of Postgraduate Medicine and Health Professions Education. Includes index. 1. Cancer-Chemotherapy-Congresses. 2. Steroid hormones-therapeutic use Congresses. 3. Hormone receptors-congresses. 4. Hormone antagonists-congresses. I. Menon, Karumathil Matathil Jayaram. II. Reel, J. R. III. Michigan, University. Dept. of Postgraduate Medicine and Health Professions Education. [DNLM: 1. Steroids-Therapeutic use-congresses. 2. Steroids-Pharmacodynamics-Congresses. 3. Neoplasms-Drug therapy-congresses. QZ267 S839 1975] RC271.H55S73 616.9'94'061 76-25873 ISBN-13: 978-1-4684-2603-8 001: 10.1007/978-1-4684-2601-4 e-isbn-13: 978-1-4684-2601-4 Proceedings of a symposium on Steroid Hormone Action and Cancer held at the University of Michigan, Ann Arbor, Michigan, October 27-29, 1975 1976 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1976 A Division of Plenum Publishing Corporation 227 West 17th Street, New York, N.Y. 10011 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher

Preface This volume is an outgrowth of a symposium held at the University of Michigan, Ann Arbor, Michigan, October 27-29, 1975. This symposium was organized to bring together basic scientists and clinicians for the purpose of exchanging new ideas and the latest information in the area of Steroid Hormone Action and Cancer. The design of the symposium included both formal plenary sessions and informal roundtable discussion groups, the chapters of this volume being drawn primarily from these proceedings. During the last quarter of a century considerable progress has been made toward understanding the molecular mechanisms involved in steroid hormone action. It now appears that the mechansim of action of the four major classes of steroid hormones is qualitatively similar. Research during the past decade has demonstrated steroid hormone receptors in a variety of normal and neoplastic tissues. Receptor-containing neoplasms have been shown to be hormone-dependent and undergo regression when treated with hormone antagonists. Natural and synthetic steroids also have been employed for many years to successfully treat various types of cancer, for example: estrogens, androgens and progestagens for breast cancer; estrogens and progestagens for prostatic carcinoma; progestagens for endometrial carcinoma; and corticoids for leukemias. All of these neoplasms have now been found to possess receptors for the steroids empirically used in their treatment. By analogy to the known relationship between estrogen receptors and the response of breast cancer to endocrine therapies, the latter observations suggest that steroid receptors may have prognostic value in deciding which neoplasms will respond to hormonal therapy. The editors would like to thank all.members of the Conference Committee for their efforts in organizing this symposium, and for serving as moderators of the roundtable discussions. We also are indebted to the Department of Postgraduate Medicine and Health Professions Education, University of Michigan, who sponsored this meeting and to the following pharmaceutical companies who provided v

vi PREFACE financial support: Ayerst, Eli Lilly, Hoffman-laRoche, McNeil, Ortho, Ciba, Geigy, Searle, Upjohn and Wyeth. The excellent cooperation and efforts of Ms. Phyllis M. Straw and Mr. Stephen Dyer and other members of the staff of Plenum Press are gratefully acknowledged. Finally, we wish to thank Mrs. Cynthia Giraud for her time, effort and excellent cooperation in typing the manuscripts.

Contents 1. 2. 3. Steroid-Induced, Steroid-Producing and Steroid Responsive Tumors.......... Roy Hertz The Etiology of Breast Cancer..... Marvin A. Rich, Philip Furmanski, Charles M. McGrath, Justin McCormick, Jose Russo and Herbert Soule Selecting Endocrine Therapy in Breast Cancer W.L. McGuire, K.B. Horwitz and M. De La Garza 1 15 28 4. The Metabolism of Steroid Hormones in Breast Cancer: A Reappraisal S.C. Brooks 36 5. 6. Fractionation of Diverse Steroid-Binding Proteins: Basic and Clinical Applications... Merry R. Sherman and Lorraine K. Miller Mammalian Progesterone Receptors: Biosynthesis, Structure, and Nuclear Binding. L.E. Faber, J. Saffran, T.H. Chen and W.W. Leavitt 51 68 7. The Mode of Action of Progestagens on Endometrial Carcinoma.. Jerry R. Reel 85 8. 9. Are Oral Contraceptives and Diethylstilbestrol (DES) Involved in Sex-Linked Cancer?... Richard A. Edgren Ragioiodinated Estrogens and Antiestrogens as Potential Imaging Agents R.E. Counsell, A. Buswink, N. Korn, M. Johnson, V. Ranade, and T. Yu vii 95 107

viii 10. The Cellular Actions of Glucocorticoids in Relation to Human Neoplasms E. Brad Thompson CONTENTS 114 11. 12. Adrenal Steroids, Membranes and Neoplasia Thomas D. Gelehrter Active Forms and Biodynamics of the Androgen Receptor in Various Target Tissues Shutsung Liao, Stephen C. Hung, John L. Tymoczko and Tehming Liang 133 139 13. The Relevance of Studies on Androgen Action to Prostatic Cancer W. Ian P. Mainwaring 152 14. Summary K.M.J. Menon Conference Committee Index. 172 176 177