Table Of ContentStructure and Function
of the Gonadotropins
BIOCHEMICAL ENDOCRINOLOGY
Series Editor: Kenneth W. McKerns
STRUCTURE AND FUNCTION OF THE GONADOTROPINS
Edited by Kenneth W. McKerns
Structure and Function
of the Gonadotropins
Edited by
Kenneth W McKerns
President
The International Society for Biochemical Endocrinology
Blue Hill Falls, Maine
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Main entry under title:
Structure and function of the gonadotropins.
(Biochemical endocrinology)
Inc1udes bibliographies and index.
1. Gonadotropin. I. McKerns, Kenneth W.
QP572.G6S83 599'.01'6 78-12372
ISBN 978-1-4684-3416-3 ISBN 978-1-4684-3414-9 (eBook)
DOI 10.1007/978-1-4684-3414-9
© 1978 Plenum Press, New York
Softcover reprint ofthe hardcover Ist edition 1978
A Divison of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
Ali rights reserved
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Contributors
J. H. Abel, Jr., Department of Physiology and Biophysics, Colorado State Uni
versity, Fort Collins, Colorado 80523
H. Abou-Issa, Department of Biochemistry, Emory University School of Medi
cine, Atlanta, Georgia 30322
Steven Birken, Department of Medicine, Columbia University College of Phy
sicians and Surgeons, New York, New York 10032
E. M. Bogdanove, Department of Physiology, Medical College of Virginia, Rich
mond, Virginia 23298
Irving Boime, Departments of Obstetrics and Gynecology, Washington Univer
sity School of Medicine, St. Louis, Missouri 63110
Elisabeth Burzawa-G~rard, Laboratoire de Physiologie Generale et Comparee
du Museum National d'Histoire NaturelIe; Laboratoire d'Endocrinologie
Comparee Associe au Centre National de la Recherche Scientifique, Paris,
France
Robert E. Canfield, Department of Medicine, Columbia University College of
Physicians and Surgeons, New York, New York 10032
T. T. Chen, Department of Physiology and Biophysics, Colorado State Univer
sity, Fort Collins, Colorado 80523
Gwen V. Childs (formerly Gwen C. Moriarty), Departments of Anatomy and Bio
logical Sciences, Northwestern University Medical School, Chicago, Illinois
60611
A. Kent Christensen, Department of Anatomy, The University of Michigan
Medical School, Ann Arbor, Michigan 48109
A. G. Davies, Department of Physiology, Medical School, Birmingham, England
M. A. Diekman, Department of Physiology and Biophysics, Colorado State Uni
versity, Fort Collins, Colorado 80523
Yves A. Fontaine, Laboratoire de Physiologie Generale et Comparee du Museum
National d'Histoire Naturelle; Laboratoire d'Endocrinologie Comparee Asso
cie au Centre National de la Recherche Scientifique, Paris, France
Jean Garnier, Laboratoire de Biochimie physique, I.N.R.A., Universite de
Paris-Sud, Orsay, France
v
vi Contributors
Linda C. Giudice, Department of Biologic a! Chemistry, University of California
School of Medicine, Los Angeles, California 90024
Jack Gorski, Departments of Biochemistry and Animal Science, University of
Wisconsin, Madison, Wisconsin 53706
F. Haour, Unite de Recherches sur Ie Controle Hormonal des Activites Cel
lulaires, Hopital Debrousse, Lyon, France
Mary Hunzicker-Dunn, Department of Biochemistry, Northwestern University
Medical School, Chicago, Illinois 60611
Richard A. Jungmann, Department of Biochemistry, Northwestern University
Medical School, Chicago, Illinois 60611
Tomasz Kuryl, Laboratory of Biochemistry and Metabolism, National Institute of
Arthritis, Metabolism and Digestive Diseases, National Institutes of Health,
Bethesda, Maryland 20014; present address: Institute of Genetics and Anima!
Breeding, Polish Academy of Sciences, Mrokow, Poland
Thomas Landefeld, Departments of Obstetrics and Gynecology, Washington
University School of Medicine, St. Louis, Missouri 63110
N. R. Lawrence, Department of Physiology, Medical School, Birmingham,
England
Janet M. Loring, Department of Biological Chemistry and Laboratory of Human
Reproduction and Reproductive Biology, Harvard Medical School, Boston,
Massachusetts 02115
Richard A. Maurer, Department of Physiology and Biophysics, University of
Iowa, Iowa City, Iowa 52242
M. C. McClellan, Department of Physiology and Biophysics, Colorado State Univer
sity, Fort Collins, Colorado 80523
Kenneth W. McKerns, Roselea House, Blue Hill Falls, Maine 04615
Susan McQueen, Departments of Obstetrics and Gynecology, Washington University
School of Medicine, St. Louis, Missouri 63110
Diana McWilliams, Departments of Obstetrics and Gynecology, Washington
University School of Medicine, St. Louis, Missouri 63110
D. D. Nansel, Department of Physiology, Medical College of Virginia, Rich
mond, Virginia 23298
G. D. Niswender, Department of Physiology and Biophysics, Colorado State
University, Fort Collins, Colorado 90523
Janet M. Nolin, Department of Physiology, Medical College of Virginia, Rich
mond, Virginia 23298
Joanne Orth, Department of Anatomy, Temple University School of Medicine,
Philadelphia, Pennsylvania 19140; present address: Division of Reproductive
Biology, Department of Obstetrics and Gynecology, Milton S. Hershey Medi
cal Center, Hershey, Pennsylvania 17033
Peter Petrusz, Department of Anatomy and Laboratory for Reproductive Biol
ogy, University of North Carolina, Chapel Hill, North Carolina 27514
John G. Pierce, Department of Biological Chemistry, University of California
School of Medicine, Los Angeles, California 90024
Contributors vii
P. Rathnam, Cornell University Medical College, New Yolk, New Yolk 10021
L. E. Reichert, Jr., Department of Biochemistry, Emory University School of
Medicine, Atlanta, Georgia 30322
J. M. Saez, Unite de Recherches sur la Controle Hormonal des Activites Cel
lulaires, Hopital Debrousse, Lyon, France
M. R. Sairam, Reproduction Research Laboratory, Clinical Research Institute of
Montreal, Montreal, Quebec, Canada; University of Montreal, Montreal,
Canada
Barbara M. Sanborn, Department of Reproductive Medicine and Biology, Uni
versity of Texas Health Science Center, Medical School, Houston, Texas
77025
B. B. Saxena, Cornell University Medical College, New Yolk, New Yolk 10021
Anna Steinberger, Department of Reproductive Medicine and Biology, The Uni
versity of Texas Health Science Center, Medical School, Houston, Texas
77025
Emil Steinberger, Department of Reproductive Medicine and Biology, Univer
sity of Texas Health Science Center, Medical School, Houston, Texas 77025
Roger T. Stone, Department of Reproduction, United States Meat Animal Re
search Center, Clay Center, Nebraska 68933
Clara M. Szego, Department of Biology, Molecular Biology Institute, and Can
cer Center, University of California, Los Angeles, California 90024
Yale J. Topper, Laboratory of Biochemistry and Metabolism, National Institute
of Arthritis, Metabolism and Digestive Diseases, National Institutes of
Health, Bethesda, Maryland 20014
Judith L. Vaitukaitis, Thorndike Memorial Laboratory, Section of Endocrinology
and Metabolism, Boston City Hospital; Department of Medicine, Boston Uni
versity School of Medicine, Boston, Massachusetts 02118
Claude A. Vil/ee, Department of Biological Chemistry and Laboratory of Human
Reproduction and Reproductive Biology, Harvard Medical School, Boston,
Massachusetts 02115
Darrell N. Ward, Department of Biochemistry, The University of Texas System
Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston,
Texas 77030
Lech Zwierzchowski, LaboratOlY of Biochemistry and Metabolism, National In
stitute of Arthritis, Metabolism and Digestive Diseases, National Institutes of
Health, Bethesda, Maryland 200 14; present address: Institute of Genetics and
Animal Breeding, Polish Academy of Sciences, Mrokow, Poland
Preface
In September of 1977 scientists from many countries met at the Asticou
Inn in Maine to present and discuss papers written especially for this
monograph. The presentations were informal and directed to the special
interests of the audience in order to generate discussions. The authors,
many of whom are pioneers and leaders in their field, then had the oppor
tunity to revise their contributions, which were brought together with the
edited discussions to form this volume.
The basic research studies presented here are important because of
the essential role of gonadotropins in regulating the ovary and testis. This
monograph will therefore be of interest to those concerned with fertility
regulation, population control, possible new methods for contraception,
and to those concerned with reproduction in domestic animals. Re
searchers in other fields may find this monograph useful, as it has been de
termined that gonadotropins are secreted by many tumors and are im
plicated in many cancers. Human choriogonadotropin also seems to be
found in most, if not all, cells of the human body. The significance of this,
however, is unknown.
The gonadotropins include human choriogonadotropin; lutropin de
rived from ovine, bovine, and human sources; prolactin; follicle
stimulating hormone; and the combination of fish gonadotropins and
mammalian hormones. Various concepts concerning the mechanism of
action of gonadotropins and the subcellular distribution of these glyco
protein hormones were presented. Much evidence was presented that
these large molecules do enter their target cells, are found in the cy
toplasm and nucleus, and have critical regulatory effects on cell metab
olism and on RNA and DNA synthesis.
The primary structure, or the amino acid sequence, of these large
polypeptide hormones is known. The folded, or tertiary, structure is un
known as are the amino acid residues involved in the active center.
ix
x Preface
I wish to thank the following who served as chairpersons of the vari
ous sessions: Harold Spies. Georges Hennen, Marian Jutisz, Dorothy
Villee, Fernand Peron, Sidney Roberts, and Robert Neher.
This meeting and monograph are part of a continuing series spon
sored by the International Society for Biochemical Endocrinology. Prior
publications in the series include: Functions of the Adrenal Cortex, Vols.
I and II; The Gonads; The Sex Steroids; and Hormones and Cancer. The
next monograph will be entitled Synthesis and Release of Adenohy
pophyseal Hormones: Cellular and Molecular Mechanisms. The meeting
for the presentation of papers and discussions will be held at the Chateau
de Seillac, Loire Valley, France.
Special thanks are due to Sally McDonell, who assisted in the prepa
ration of the index, typed the discussions, and acted as general secretary
for the great amount of correspondence necessary in the organization of
the meeting and monograph.
Kenneth W. McKems
Blue Hill Falls, Maine
Contents
1
Mechanism of Action of Gonadoptropins and the
Regulation of Gene Expression 1
Richard A. Jungmann and Mary Hunzicker-Dunn
I. Introduction 1 • 2. Development of the cAMP-Protein Kinase System in the Neo
natal Rat Ovary 4 • 3. Cyclic-AMP-Dependent Ovarian Nuclear Protein Kinase 8
• 4. Nuclear Translocation of Ovarian Cytoplasmic cAMP-Dependent Protein Kinase
Mechanism of Translocation 8 • 5. Functional Importance of Protein Kinase Trans
location 13 • 6. Correlation between Gonadotropin Action and Ovarian Nuclear Activ
ity 15 • 7. Conclusion 19 • Discussion 20 • References 24
2
Chemical Approaches to the Structure-Function
Relationships of Luteinizing Hormone (Lutropin) 31
Darrell N. Ward
3
Structural and Immunochemical Properties of
Human Choriogonadotropin 47
Steven Birken and Robert E. Canfield
I. Introduction 47 • 2. Purification 48 • 3. Structure 51 • 4. Carbohydrate Func
tion 55 • 5. Synthesis 57 • 6. Immunochemistry and Immunoassay 60 • 7. Bio
logical Activities Present in "Crude" and "Purified" hCG 67 • Discussion 72
• References 75
xi