Hormonal Control of the Hypothalamo-Pituitary-Gonadal Axis BIOCHEMICAL ENDOCRINOLOGY Series Editor: Kenneth W. McKerns STRUCTURE AND FUNCTION OF THE GONADOTROPINS Edited by Kenneth W. McKerns SYNTHESIS AND RELEASE OF ADENOHYPOPHYSEAL HORMONES Edited by Marian Jutisz and Kenneth W. McKerns REPRODUCTIVE PROCESSES AND CONTRACEPTION Edited by Kenneth W. McKerns HORMONALLY ACTIVE BRAIN PEPTIDES: Structure and Function Edited by Kenneth W. McKerns and Vladimir Pantie REGULATION OF GENE EXPRESSION BY HORMONES Edited by Kenneth W. McKerns REGULATION OF TARGET CELL RESPONSIVENESS, Volumes 1 and 2 Edited by Kenneth W. McKerns, Asbjflrn Aakvaag, and Vi dar Hansson HORMONAL CONTROL OF THE HYPOTHALAMO-PITUITARY GONADAL AXIS edited by Kenneth W. McKerns and Zvi Naor Hormonal Control of the Hypothalamo- Pituitary-Gonadal Axis Edited by Kenneth W McKerns International Foundation jor Biochemical Endocrinology Blue Hill Falls, Maine and Zvi Naor Weizmann Institute oj Science Rehovot, Israel Springer Science+Business Media, LLC Library of Congress Cataloging in Publication Data Main entry under title: Hormonal control of the hypothalamo-pituitary-gonadal axis. (Biochemical endocrinology) "Proceedings of the eleventh annual meeting of the International Foundation for Biochemical Endocrinology, held October 2-7, 1983, at the Weizmann Institute of Science, Rehovot, Israel"-T.p. verso. Includes bibliographical references and index. I. Hyptothalamo-hypophyseal system - Congresses. 2. Hypothalamic hormones Congresses. 3. Gonadotropin-Congresses. I. McKerns, Kenneth W. II. Naor, Zvi. III. International Foundation for Biochemical Endocrinology. IV. Series. [DNLM: 1. Hypothalamo-Hypophyseal System-physiology-congresses. 2. Pituitary Hormone Releasing Hormones-physiology-congresses. IN6% 11th 1983h / WK 515 1588 I 983h) QP188.H9H67 1984 599'.01'42 84-13415 ISBN 978-1-4684-9962-9 ISBN 978-1-4684-9960-5 (eBook) DOI 10.1007/978-1-4684-9960-5 Proceedings of the Eleventh Annual meeting of the International Foundation for Biochemical Endocrinology, held October 2-7, 1983, at the Weizmann Institute of Science. Rehovot, Israel © 1984 Springer Science+Husiness Media New York Originally published by Plenum Press, New York and London in 1984 Softcover reprint of the hardcover 1st edition 1984 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 The eleventh monograph and meeting of the Foundation on "Hormon al Control of the Hypothalamo-Pituitary-Gonadal Axis" was held in October 1983 at the Weizmann Institute of Science. This monograph honors the memory of Professor Hans R. Lindner, a productive and innovative scientist greatly respected and admired by his col leagues. When addressing the opening session I remarked that my impres sion of the Weizmann Institute was one or two large buildings hous ing the various departments. This was my first visit to Israel and I was overwhelmed by the beautiful semi-tropical gardens of the in stitute, in a setting of shrubs and trees, orange groves and flow ers. Sited among this seventy-five acres are over fifty buildings and residential areas for the staff and visiting scientists. I saw pictures of this area when Dr. Chaim Weizmann founded in 1934, the Daniel Sieff Research Institute, the forerunner of the Weizmann In stitute. The site was sand dunes without a blade of grass. That the desert shall bloom is illustrative of the progress made in Is rael. The topics of the monograph are grouped into twelve sections. They are: "Neuroendocrine Control of Gonadotropin Secretion," "Mo lecular Aspects of GnRH Biosynthesis, Release and Degradation," "GnRH Receptors and Action in the Pituitary," "Secretory Processes in the Pituitary," "Gonadotropin Antagonists," "Endocrine Regula tion 0 f Ovarian Functions," "Prolactin," "Hormones and Gene Expres sion," "Regulation of Testicular Function," "Extrapituitary Effects of GnRH," "Interaction of Opiates and Gonadotropins," "GnRH Ana logs: Clinical Uses in the Management of Fertility and Cancer." The chairpersons for the sessions were B. Kerdelhue, A. Beloff Chain, S.M. McCann, D. Kanazir, M. Fridkin, M. Aubert, Z. Naor, J. de Konig, M. Dufau, Y. Orly, G. Ross, B. Eckstein, B. Lunenfeld, R. Shalgi, A. Tixier-Vidal, M. Ben-David, A.M. Kaye, I. Gozes, K. Catt, E. Bedrak, B. Cooke, Z. Laron, R. Sharpe, D. Ayalon, P.F. Kraicer, J. Sandow, H. Zakut, S. Segal and G. Leyendecker. This monograph represents an interdisciplinary approach to the v vi PREFACE problem of regulation of gonadotropin secretion and action. Mor phological, physiological, clinical and biochemical aspects are re viewed, with emphasis on recent findings. This volume reviews the state of the art in the field of hypo thalamo-pituitary-gonadal axis and is relevant to endocrinologists, reproductive biologists, obstetricians and gynecologists. The twelfth meeting and monograph of the Foundation will be held in September at Caxtat, near Dubrovnik, Yugoslavia. Professor Vla dimir Pantie will be organizer of the local arrangements. The top ic will be "Neuroendo crine Correlates of Stress." Kenneth W. McKerns Zvi Naor ACKNOWLEDGMENTS The Editors express their thanks to the Organizing Committee of the Meeting, consisting of: Nava Dekel, Fortune Kohen, Yitzhak Koch, Zvi Naor (Chairman) and Uriel Zor. The Meeting was supported by grants from: The Israel Academy of Sciences and Humanities; the Israel National Council for Research and Development; The Israel Ministry of Health; The Maurice and Gabriela Goldschleger Conference Foundation at the Weizmann Insti tute of Science; The University of Tel-Aviv; The Ben-Gurion Uni versity of the Negev; The Israel Society of Endocrinology; Biotech nology General (Israel) Ltd., Rehovot; Eldan Electronic Instrument Co. Ltd., Jerusalem; Inter-Yeda Ltd., Nes-Ziona; Miles-Yeda Ltd., Rehovot; Fering Sweden; Organon International B.V., The Netherlands; and Schering Aktiengesellschaft, West Germany. vii S Y XI GA LOL OA ND RIA CN OO DG NY- ER L A AT CUI HEMIO-PIT983 CM1 OA BIL7, R HA2- OT FOR PE N YB OHO ATIHE OCT DT N UF OO F L L O AR NT OON TIC A NL RA NTEMON IR O H CONTENTS Dedication. • • • • • • • • • • • 1 NEUROENDOCRINE CONTROL OF GONADOTROPIN SECRETION Role of Peptides in the Control of Gonadotropin Secretion • • • • • • • • • • • • • • • • • • • • • • •• 3 S.M. McCann, G.D. Snyder, S.R. Ojeda, M.D. Lumpkin, A. Ottlecz, and W.K. Samson Molecular Aspects of the Release of Luteinizing Hormone Releasing Hormone (LHRH) from Hypothalamic Neurons. • • • • • • • • • • • • • • • • • • 27 A. Barnea Role of Pep tides in the Regulation of Gonadotropin and Prolactin Secretion • • • • ••••• 39 M. Motta, P. Falaschi, S. Zoppi, and L. Martini Estrous Cycle Dependent Modulation of Muscarinic Cholinergic Receptors in the Hypothalamus and Adenohypophysis • • • • • • • • • • • • • 55 M. Sokolovsky, E. Moscona-Amir and Y. Egozi HOLECULAR ASPECTS OF GnRH BIOSYNTHESIS, RELEASE, AND DEGREADATION Hormones and Other Messenger Molecules: An Approach to Unity. . . • • • • • • .. • • • • • • • . • •• 71 J. Roth, D. LeRoith, J. Shiloach and C. Rabinowitz Regulation of the Synthesis, Release and Action of Hypothalamic Luteinizing Hormone Releasing Hormone • • • • • • • • 89 G. Fink, A. Curtis, and V. Lyons . . . . . . . . . . . . . Degradation of LH-RH. • • • • 101 K. Bauer and B. Horsthemke ix x CONTENTS Degradation of Luteinizing Hormone-Releasing Hormone by Rat Pituitary Plasma Membrane Associated Enzymes. • . •. . ........... . 115 Y. Koch, S. Elkabes and M. Fridkin GnRH RECEPTORS AND ACTION IN THE PITUITARY GnRH Receptors: Identification, Localization, and Implications for Biological Function . . . . 127 E. Hazum Physiological Regulation of Pituitary GnRH Receptors . . . 141 R.N. Clayton, S.I. Naik, L.S. Young, and H.M. Charlton GnRH Recpetor Microaggregation: Regulation of Gonadotropin Release, GnRH Receptors, and Gonadotrope Responsiveness . . . • . . .. 153 P.M. Conn, D.C. Rogers, S.G. Seay, L. Jennes, H. Jinnah, M. Bates, D. Clapper and D. Luscher SECRETORY PROCESSES IN THE PITUITARY Recent Progress in Cell Biology of Secretory Process in Anterior Pituitary Cells . . . . . . . . . 169 A. Tixier-Vidal and C. Tougard Fluidity of Gonadotropin Storage in Cycling Female Rats ..•.......•......... 181 G.V. Childs Regulation of Peptide Hormone Receptors in the Pituitary-Gonadal Axis: Receptors to Gonadotropins and Gonadotropin Releasing Hormone . 199 A. Amsterdam GONADOTROPIN ANTAGONISTS Strategies for the Inhibition of Gonadotropin Action • ............. . 219 M.R. Sairam The Role of Carbohydrate Moiety of Gonadotropin Molecule in Transduction of Biological Signal. 235 U. Zor, M.R. Sairam, P. Shentzer, A. Azrad, and A. Amsterdam