Modes of Action of GnRH and GnRH Analogs

387 Pages·1992·9.73 MB·English

by  Randall W. Whitcomb

Serono Symposia, USA
Norwell, Massachusetts
FERTILIZA TION IN MAMMALS
Edited by Barry D. Bavister, Jim Cummins,
and Eduardo R.S. Roldan
FOLLICLE STIMULATING HORMONE: Regulation of Secretion
and Molecular Mechanisms of Action
Edited by Mary Hunzicker-Dunn and Neena B. Schwartz
GAMETE PHYSIOLOGY
Edited by Ricardo H. Asch, Jose P. Balmaceda,
and Ian Johnston
GLYCOPROTEIN HORMONES: Structure, Synthesis, and Biologic
Function
Edited by William W. Chin and Irving Boime
GROWTH FACTORS IN REPRODUCTION
Edited by David W. Schomberg
THE MENOPAUSE: Biological and Clinical Consequences of Ovarian
Failure: Evaluation and Management
Edited by Stanley G. Korenman
MODES OF ACTION OF GnRH AND GnRH ANALOGS
Edited by William F. Crowley, Jr., and P. Michael Conn
NEUROENDOCRINE REGULATION OF REPRODUCTION
Edited by Samuel S.C. Yen and Wylie W. Vale
SIGNALING MECHANISMS AND GENE EXPRESSION
IN THE OVARY
Edited by Geula Gibori
UTERINE CONTRACTILITY: Mechanisms of Control
Edited by Robert E. Garfield
Serono Symposia, USA
Norwell, Massachusetts
William F. Crowley, Jr. P. Michael Conn
Editors
Modes of Action
of GnRH and
GnRH Analogs
With 117 Figures
Springer-Verlag
New York Berlin Heidelberg London Paris
Tokyo Hong Kong Barcelona Budapest
William F. Crowley, Jr., M.D. P. Michael Conn, Ph.D.
Reproductive Endocrine Unit Department of Pharmacology
Department of Medicine University of Iowa College of
Massachusetts General Hospital Medicine
Boston, MA 02114 Iowa City, IA 52242-1109
USA USA
Proceedings of the Symposium on Modes of Action of GnRH and GnRH Analogs, sponsored by Serono
Symposia, USA, held February 26 to March 2, 1991, in Scottsdale, Arizona.
For infonnation on previous volumes, please contact Serono Symposia, USA.
Library of Congress Cataloging-in-Publication Data
Modes of action of GnRH and GnRH analogslWilliam F. Crowley, Jr., P.
Michael Conn, editors.
p. cm.
"Proceedings of the Symposium on Modes of Action of GnRH and GnRH
Analogs, sponsored by Serono Symposia, USA, held February 26 to
March 2,1991, in Scottsdale, Arizona."-T.p. verso.
Includes bibliographical references and indexes.
ISBN-I3:978·1-4612· 7718· 7
1. Luteinizing hormone releasing hormone-Mechanism of action
Congresses. 2. Luteinizing hormone releasing hormone-Derivatives
Mechanism of action-Congresses. l. Crowley, William F. (William
Francis) II. Conn, P. Michael. III. Serono Symposia, USA.
IV. Symposium on Modes of Action of GnRH and GnRH Analogs (1991:
Scottsdale, Ariz.)
[DNLM: 1. Gonadorelin-analogs & derivatives-congresses.
2. Gonadorelin-physiology-congresses. 3. Gonadorelin-therapeutic
use-congresses. WK 515 M691 1991]
QP572.L85M63 1992
612.6-dc20
DNLMIDLC 92-2157
Printed on acid-free paper.
© 1992 Springer-Verlag New York, Inc.
Softcover reprint of the hardcover 1st edition 1992
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987654321
ISBN-I3:978·1-4612-7718· 7 e-ISBN-13:978·1·4612·2916·2
DOl: 10.10071978-1·4612·2916·2
SYMPOSIUM ON MODES OF ACTION OF GnRH AND
GnRH ANALOGS
Scientific Committee
P. Michael Conn, Ph.D., Cochairman
University of Iowa College of Medicine
William F. Crowley, Jr., M.D., Cochairman
Massachusetts General Hospital
and Harvard Medical School
Organizing Secretary
L. Lisa Kern, Ph.D.
Serono Symposia, USA
100 Longwater Circle
Norwell, Massachusetts
Preface
Since the awarding of the Nobel Prize to Drs. Guillemin and Schally iJ)
1971 for isolation and chemical characterization of gonadotropin releasing
hormone, we have experienced a remarkable period of growth of interest
in this hormone. The last 20 years have been characterized by a swift
translation of basic science discovery into clinical utility. Approval of
GnRH and its analogs for treatment of prostate cancer, endometriosis,
and precocious puberty and for induction of ovulation indicate the range
of usefulness of these agents.
In order to bring together the leaders in the basic and clinical science
of GnRH, a conference was organized on "Modes of Action of GnRH
and GnRH Analogs" and held in Scottsdale, Arizona, February 26 to
March 2, 1991. The presentations, given as chapters in this volume, show
both the advances in the body of information in this discipline and the
efforts underway to reduce basic science to clinical practice. The audience
was a combination of representatives from universities, government,
industry, and physicians in practice. The lively discussions and insightful
questions indicated the interest in the topics discussed and frequently
served to catalyze planned interactions of the meeting participants.
The organizers are grateful to the speakers and poster presenters for
their contributions and for the timely preparations of the manuscripts
included in the present volume. We are also thankful to the staff of
Serono Symposia, USA, for the organizational skills and support that
allowed the meeting organizers to focus on the science and medicine
presented.
WILLIAM F. CROWLEY, JR.
P. MICHAEL CONN
vii
Contents
Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v.ii
Contributors...................... .. .. ........................................ ..... xiii
Part I. Overview of GnRH Secretion and Mechanism of Action
1. Critical Determinants of GnRH-Gonadotrope Interactions in
the Human.................................................................. 3
RANDALL W. WHITCOMB AND WILLIAM F. CROWLEY, JR.
2. Gonadotropin Releasing Hormone and Its Actions.............. 26
TIM D. BRADEN AND P. MICHAEL CONN
3. Regulation of Gonadotropin Gene Expression by
Gonadotropin Releasing Hormone................................... 55
JOHN C. MARSHALL, ALAN C. DALKIN, AND
DANIEL J. HAISENLEDER
Part II. Molecular and Developmental Control of
GnRH Expression
4. Molecular Studies of GnRH
Part I. Nonresponse of 5' Flanking Region of Rat GnRH
Gene to Estrogen In Vitro or In Vivo............................... 69
C.T. BOND, R. SEAL, R. SIMERLY, AND J.P. ADELMAN
Part II. Isolation and Characterization of Teleost
PreproGnRH Encoding cDNA from the African Cichlid
Haplochromis burtoni .................................................... 79
C.T. BOND, R. FERNALD, R. FRANCIS, AND J.P. ADELMAN
5. Characterization, Expression, and Estradiol Regulation of
the Human GnRH Gene................................................ 85
SALLY RADOVICK, FREDRIC E. WONDISFORD, SUSAN WRAY,
CHRISTINE TICKNOR, YUKO NAKAYAMA, GORDON B. CUTLER, JR.,
BRUCE D. WEINTRAUB, HEINER WESTPHAL, AND ERIC LEE
ix
x Contents
6. Control of Rat Gonadotropin Releasing Hormone Promoter
Activity in Placental Cells............................................... 106
MARGARET E. WIERMAN, WEI SUN, CHUN WANG,
DAVID F. GORDON, AND WILLIAM W. WOOD
7. Cellular and Molecular Aspects of LHRH Secretion
and Bioactivity............................................................. 116
ANDRES NEGRO-VILAR, WILLIAM WETSEL, MARCELO VALEN<;A,
ISTVAN MERCHENTHALER, FRANCISCO LOPEZ, ZSOLT LIPOSITS,
MELVIN CHING, RICHARD WEINER, AND PAMELA MELLON
8. Theories of Luteinizing Hormone Releasing Hormone
Neuronal Migration: Mechanisms and
Biological Importance.................................................... 131
MARLENE SCHWANZEL-FuKUDA AND DONALD W. PFAFF
9. Functional GnRH Neuronal Transplants in the
Hypogonadal Mouse ..................................................... 144
MARIE J. GIBSON, YOUICHI SAITOH, GREGORY M. MILLER, AND
ANN-JUDITH SILVERMAN
Part III. GnRH Physiology: Animal Models
10. GnRH Subgroups: A Microarchitecture ............................ 161
J.e. KING AND B.S. RUBIN
11. Exactitude in the Relationship Between GnRH and
LH Secretion................................................ . . .. ..... ... .. . 179
I.J. CLARKE
12. Studies of LHRH Secretion into the Hypophyseal Portal
Blood of the Ram: Gonadal Regulation of LH Secretion Is
Exerted Mainly at the Hypothalamic Level........................ 193
ALAIN CARATY, PHILIPPE BOUCHARD, AND MICHEL R. BLANC
13. Gonadal Feedback Regulation of LHRH Release and
Actions in the Rat.............................................. ........... 211
JANICE H. URBAN, JOHN M. MEREDITH,
ANGELA e. BAUER-DANTOIN, FRANK J. STROBL, AND
JON E. LEVINE
Contents xi
14. Gonadotropin Releasing Hormone Gene Expression During
the Rat Reproductive Cycle............................................ 223
OK-KYONG PARK, SAJIV GUGNEJA, AND KELLY E. MAyo
15. The Preovulatory Surge of Gonadotropin Releasing
Hormone.................................................................... 241
FRED J. KARSCH, SUZANNE M. MOENTER, AND ALAIN CARATY
16. Regulation of Pulsatile LHRH Release in Primates.............. 256
EI TERASAWA AND ANDREA C. GORE
Part IV. GnRH Antagonists
17. An Overview of GnRH Antagonist Development:
Two Decades of Progress ............................................... 277
MARVIN J. KARTEN
18. GnRH Antagonists in Men............................................. 298
SPYROS N. PAVLOU
19. Use of GnRH Antagonists as Physiologic Probes in
the Female ............ ........ ............ .................................. 310
JANET E. HALL AND WILLIAM F. CROWLEY, JR.
20. Gonadotropin Releasing Hormone Antagonist Plus
Testosterone: A Potential Male Contraceptive.................... 322
WILLIAM J. BREMNER, CARRIE J. BAGATELL, AND
ROBERT A. STEINER
21. GnRH Antagonists: Primate Models for
Clinical Indications ....................................................... 332
KEITH GORDON, DOUGLAS R. DANFORTH,
ROBERT F. WILLIAMS, AND GARY D. HODGEN
22. Use of Gonadotropin Releasing Hormone Analogs to
Influence Sexual and Behavioral Development.................... 347
DAVID R. MANN, KENNETH G. GOULD, AND KIM WALLEN
Author Index...................................................................... 371
Subject Index...................................................................... 373
Contributors
J.P. ADELMAN, Vollum Institute, Oregon Health Sciences University,
Portland, Oregon, USA.
CARRIE J. BAGATELL, Medical Service, Veterans Affairs Medical
Center, Department of Medicine, Population Center for Research in
Reproduction, and the Regional Primate Research Center, University of
Washington, Seattle, Washington, USA.
ANGELA C. BAUER-DANTOIN, Department of Neurobiology and
Physiology, Northwestern University, Evanston, Illinois, USA.
MICHEL R. BLANC, Station de Physiologie de la Reproduction, Institut
National de la Recherche Agronomique, 37380 Nouzilly, France.
C.T. BOND, Vollum Institute, Oregon Health Sciences University,
Portland, Oregon, USA.
PHILIPPE BOUCHARD, Service d'Endocrinologie, Hopital de Bicetre, 94270
Le Kremlin Bicetre, France.
TIM D. BRADEN, Department of Pharmacology, University of Iowa
College of Medicine, Iowa City, Iowa, USA.
WILLIAM J. BREMNER, Medical Service, Veterans Affairs Medical
Center, Department of Medicine, Population Center for Research in
Reproduction, and the Regional Primate Research Center, University of
Washington, Seattle, Washington, USA.
ALAIN CARATY, Station de Physiologie de la Reproduction, Institut
National de la Recherche Agronomique, 37380 Nouzilly, France.
MELVIN CHING, Laboratory of Molecular and Integrative Neurosciences,
National Institute of Environmental Health Sciences, National Institutes
of Health, Research Triangle Park, North Carolina, USA.
xiii