Table Of ContentSTEROID DYNAMICS
Proceedings of the Symposium
on the Dynamics of Steroid Hormones
held in Tokyo, May, 1965
Edited by
GREGORY PINCUS TAKESHI NAKAO
WORCESTER FOUNDATION FOR DEPARTMENT OF PHARMACOLOGY
EXPERIMENTAL BIOLOGY JIKEI UNIVERSITY SCHOOL OF MEDICINE
SHREWSBURY TOKYO, JAPAN
MASSACHUSETTS
JAMES F. TAIT
WORCESTER FOUNDATION FOR
EXPERIMENTAL BIOLOGY
SHREWSBURY
MASSACHUSETTS
1966
ACADEMIC PRESS New York and London
COPYRIGHT © 1966, BY ACADEMIC PRESS INC.
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List of Contributors
Numbers in parentheses indicate the pages on which the authors' contributions begin.
Yoshitaka Araki, First Department of Internal Medicine, Faculty of
Medicine, University of Tokyo, Tokyo, Japan (463)
C. W. Bardin, Endocrinology Branch, National Cancer Institute, Bethes-
da, Maryland (111)
Jo Ann Brueggemann, Department of Biological Chemistry and Depart-
ment of Surgery, Harvard Medical School, and Peter Bent Brigham
Hospital, Boston, Massachusetts (159)
C. A. Camargo,^ Department of Medicine, Stanford University School of
Medicine, Palo Alto, California (341)
R. A. Chevaie, Department of Medicine, Stanford University School of
Medicine, Palo Alto, California (341)
V. Colucci, Ben May Laboratory for Cancer Research, University of
Chicago, Chicago, Illinois (133)
R. De Hertogh,2 Department of Biological Chemistry and Department of
Surgery, Harvard Medical School, and Peter Bent Brigham Hos-
pital, Boston, Massachusetts (159)
E. R. DeSombre, Ben May Laboratory for Cancer Research, University
of Chicago, Chicago, Illinois (133)
Richard P. Doe, Minneapolis Veterans Administration Hospital, Meta-
bolic Research Section, and Department of Medicine, University
of Minnesota Medical School, Minneapolis, Minnesota (63)
1 Present address: Universidad del Valle Medical School, Call, Colombia.
2Present address: Hospital St. Pierre, Louvain, Belgium.
V
Vi LIST OF CONTRIBUTORS
A. J. Dowdy, Department of Medicine, Stanford University School of
Medicine, Palo Alto, California (341)
Isidore S. Edelman,^ Cardiovascular Research Institute and Department
of Medicine, University of California School of Medicine, San
Francisco, California (551)
J. W. Flesher, Ben May Laboratory for Cancer Research and Department
of Physiology, University of Chicago, Chicago, Illinois (133)
G. N. Gupta, Ben May Laboratory for Cancer Research and Department
of Physiology, University of Chicago, Chicago, Illinois (133)
Erlio Gurpide, Departments of Biochemistry and of Obstetrics and Gyne-
cology, College of Physicians and Surgeons, Columbia University,
New York, New York (531)
E. W. Hancock, Department of Medicine, Stanford University School of
Medicine, Palo Alto, California (341)
Kogo Hiraga, Department of Pharmacology, Jikei University School of
Medicine, Tokyo, Japan (179)
R. Horton,^ Worcester Foundation for Experimental Biology, Shrews-
bury, Massachusetts (393)
H. Ibayashi, Third Department of Medicine, University of Tokyo Faculty
of Medicine, Kongo, Tokyo, Japan (91)
Shogo Ichii, National Institute of Radiological Science, Chiba, Japan (357)
Minoru Inaba, Department of Pharmacology, Jikei University School of
Medicine, Tokyo, Japan (179)
H. I. Jacobson, Ben May Laboratory for Cancer Research and Depart-
ment of Physiology, University of Chicago, Chicago, Illinois (133)
E. V. Jensen, Ben May Laboratory for Cancer Research and Department
of Physiology, University of Chicago, Chicago, Illinois (133)
P. W. Jungblut, Ben May Laboratory for Cancer Research and Depart-
ment of Physiology, University of Chicago, Chicago, Illinois (133)
Masaaki Kashima, First Department of Internal Medicine, Faculty of
Medicine, University of Tokyo, Tokyo, Japan (463)
Junzo Kato, Department of Obstetrics and Gynecology, School of Medi-
cine, University of Tokyo, Tokyo, Japan (303)
^Present address: Polymer Department, Weizmann Institute of Science, Rehovoth, Israel.
^Present address: Department of Medicine, University of California at Los Angeles Center
for the Health Sciences, Los Angeles, California.
LIST OF CONTRIBUTORS vii
Tatsuo Kato, First Department of Internal Medicine, Faculty of Medi-
cine, University of Tokyo, Tokyo, Japan (463)
Masazumi Kawakami, Department of Physiology, Yokohama Uni-
versity, School of Medicine, Yokohama, Japan (237)
Shigeru Kobayashi, National Institute of Radiological Science, Chiba,
Japan (357)
Takashi Kobayashi, Department of Obstetrics and Gynecology, School
of Medicine, University of Tokyo, Tokyo, Japan (303)
Takuro Kobayashi, Department of Obstetrics and Gynecology, School
of Medicine, University of Tokyo, Tokyo, Japan (303)
Tsuyoshi Kono, Second Division, Department of Internal Medicine,
Kyoto University School of Medicine, Kyoto, Japan (429)
S. G. Korenman, Endocrinology Branch, National Cancer Institute,
Bethesda, Maryland (111)
K. R. Laumas,^ Department of Biological Chemistry and Department of
Surgery, Harvard Medical School and Peter Bent Brigham Hos-
pital, Boston, Massachusetts (159)
Seymour Lieberman, Departments of Biochemistry and of Obstetrics
and Gynecology, College of Physicians and Surgeons, Columbia
University, New York, New York (531)
M. B. Lipsett, Endocrinology Branch, National Cancer Institute, Bethes-
da, Maryland {\\7)
J. A. Luetscher, Department of Medicine, Stanford University School
of Mtdicine, Palo Alto, California (341)
Michio Matsuba, Department of Pharmacology, Jikei University School
of Medicine, Tokyo, Japan (357)
K. Matsumoto, Department of Pathology, Osaka University Medical
School, Osaka, Japan (379)
Hiroshi Minaguchi, Department of Obstetrics and Gynecology, School
of Medicine, University of Tokyo, Tokyo, Japan (303)
Tadashi Miyake, Second Division, Department of Internal Medicine,
Kyoto University School of Medicine, Kyoto, Japan (429)
Tatsuo Miyazaki, First Department of Internal Medicine, Faculty of
Medicine, University of Tokyo, Tokyo, Japan (463)
5Present address: All India Institute of Medical Sciences, New Delhi, India.
Viii LIST OF CONTRIBUTORS
K. Motohashi, Third Department of Medicine, University of Tokyo
Faculty of Medicine, Hongo, Tokyo, Japan (91)
S. Murakawa, Third Department of Medicine, University of Tokyo
Faculty of Medicine, Hongo, Tokyo, Japan (91)
M. Nakamura, Third Department of Medicine, University of Tokyo
Faculty of Medicine, Hongo, Tokyo, Japan (91)
Takeshi Nakao, Department of Pharmacology, Jikei University School of
Medicine, Tokyo, Japan (179)
H. G. Neumann,^ Ben May Laboratory for Cancer Research and De-
partment of Physiology, University of Chicago, Chicago, Illinois
(133)
G. W. Nokes, Department of Medicine, Stanford University School of
Medicine, Palo Alto, California (341)
K. Okano, Department of Pathology, Osaka University Medical School,
Osaka, Japan 019)
M. R. J. Pearlman, Department of Biological Chemistry and Department
of Surgery, Harvard Medical School, and Peter Bent Brigham Hos-
pital, Boston, Massachusetts (159)
William H. Pearlman, Department of Biological Chemistry and Depart-
ment of Surgery, Harvard Medical School, and Peter Bent Brigham
Hospital, Boston, Massachusetts (159)
H. Rosenthal, Roswell Park Memorial Institute, Buffalo, New York (1)
N. N. Saha,^ Ben May Laboratory, University of Chicago, Chicago,
Illinois (133)
Leo T. Samuels, Department of Biological Chemistry, University of Utah
College of Medicine, Salt Lake City, Utah (385)
Avery A. Sandberg, Roswell Park Memorial Institute, Buffalo, New York
(1)
S. L. Schneider, Roswell Park Memorial Institute, Buffalo, New York (1)
Ulysses S. Seal, Minneapolis Veterans Administration Hospital, Metabolic
Research Section, and Department of Biochemistry, University of
Minnesota, Minneapolis, Minnesota (63)
T. Seki, Department of Genetics, Osaka University Medical School,
Osaka, Japan (379)
6 Present address: Max-Planck Institut far Biochemie, Postschliessfach, Germany.
^Present address: Physiology and Hormones Section, Food and Drug Laboratories, Na-
tional Health and Welfare, Ottawa, Ontario, Canada.
LIST OF CONTRIBUTORS ix
Mikio Shikita, National Institute of Radiological Science, Chiba, Japan
(493)
Kyutaro Shimizu, Department of Biochemistry, Tottori University,
School of Medicine, Yonago, Japan (481)
D. Shiplacoff, Ben May Laboratory for Cancer Research, University of
Chicago, Chicago, Illinois (133)
W. Roy Slaunwhite, Jr., Roswell Park Memorial Institute, Buffalo, New
Yorkil)
Sylvia Smith, Ben May Laboratory for Cancer Research, University of
Chicago, Chicago, Illinois (133)
J. F. Tail, Worcester Foundation for Experimental Biology, Shrewsbury,
Massachusetts (393)
Hiroo Takikawa, Department of Pharmaceutical Chemistry, Institute of
Endocrinology, Gunma University, Maebashi, Japan (217)
Bun-ichi Tamaoki, National Institute of Radiological Science, Chiba,
Japan (493)
T. Tanioka, Third Department of Medicine, University of Tokyo Faculty
of Medicine, Hongo, Tokyo, Japan (91)
Ei Terasawa, Department of Physiology, Yokohama University, School
of Medicine, Yokohama, Japan (237)
Shoichi Tsuchihashi, Department of Physiology, Yokohama University,
School of Medicine, Yokohama, Japan (237)
T. Uozumi, Department of Surgery, Osaka University Medical School,
Osaka, Japan (379)
Yoshiko Urata, Department of Pharmacology, Jikei University School
of Medicine, Tokyo, Japan (179)
H. Wilson, Endocrinology Branch, National Cancer Institute, Bethesda,
Maryland {Ul)
T. Yamaji, Third Department of Medicine, University of Tokyo Faculty
of Medicine, Hongo, Tokyo, Japan (91)
Kazuo Yamanaka, Department of Physiology, Yokohama University,
School of Medicine, Yokohama, Japan (237)
Osamu Yokota, First Department of Internal Medicine, Faculty of Medi-
cine, University of Tokyo, Tokyo, Japan (463)
Teruya Yoshimi, Second Division, Department of Internal Medicine,
Kyoto University School of Medicine, Kyoto, Japan (429)
Preface
The papers published in this volume were presented at a conference
held in Tokyo, May 9-15, 1965. The conference was conducted under
the United States-Japan Cooperative Science Program sponsored jointly
by the National Science Foundation and the Japanese Society for the
Promotion of Science. The coordinators of the conference were Profes-
sor Takeshi Nakao of Japan and Professor Gregory Pincus of the United
States. The latter was unable to attend the meeting, and in his stead
Professor Leo Samuels very kindly acted as co-chairman. These seminars
under the Cooperative Program are to "have as their primary purpose
the fostering of contacts between scientists in the fields concerned,
looking toward continued communication between the participants
through later visits, correspondence, and possible mutual research
efforts." This book is obvious evidence of the first steps in the process
of communication and discussion. The selection by the coordinators of
the area of steroid dynamics as the subject of choice represents the
culmination of two years of interchange and planning.
For many years studies of steroid dynamics in vivo lacked the sophisti-
cation of analogous investigations in many other fields such as those in
carbohydrate and protein metabolism. Difficulty of analysis usually pre-
cluded extensive serial sampling and assay of plasma steroids. This
barrier has now been overcome, and the intense current interest in the
field is shown by the papers of Drs. Kono, Nakao, Samuels, Lipsett,
Pearlman, Araki, Luetscher, Lieberman, and Tait, and their co-workers,
which encompass studies in man on nearly every known steroid hormone.
The inertia in such dynamic systems is determined to a major extent by
the binding of steroids to proteins; the papers of Drs. Sandberg, Taki-
kawa, and Seal, and their co-workers deal with this field.
Application of theory to studies of steroid dynamics in biosynthetic
systems has not been so extensive, but the papers of Drs. Nakao, Mat-
suba, Shimizu, Tamaoki, and Ibayashi show the promising current in-
terest in Japan in this aspect of the field.
The investigation of uptake of steroids into target tissues will un-
doubtedly make a contribution to our knowledge of the mode of action
xi
Xii PREFACE
of hormones as shown by the papers of Drs. Edelman, Pearlman, Koba-
yashi, Jensen, and Kawakami, and their co-workers. A paper by Pro-
fessor Samuels, which was followed by extensive discussion, also
covered this aspect, but due to unavoidable circumstances it does not
appear in this volume; however, his paper on in vivo dynamics, which
was not presented in Tokyo, is substituted for it.
The serious and careful efforts of the invited participants are much
appreciated, as are the efforts made in their behalf by Dr. Norman P.
Neureiter for the National Science Foundation. The superb hospitality
extended to the participants from the United States by the Japanese
hosts cannot be too highly praised.
There are difficulties in recording and editing discussions of papers
in a bilingual conference, and whatever success we have had in this
direction is largely due to the excellent interpreters in Tokyo and to the
work of Mrs. Mina Rano and Dr. Masatoshi Okamoto in Shrewsbury.
August, 1966 T. NAKAO
G. PiNCUS
J. F. TAIT
Protein-Steroid Interactions and Their Role in the
Transport and Metabolism of Steroids*
AVERY A. SANDBERG, H. ROSENTHAL, S. L. SCHNEIDER,
AND W. ROY SLAUNWHITE, JR.
Roswell Park Memorial Institute, Buffalo, New York
I. Introduction
Molecular interactions below the covalent level have been recognized
as important phenomena in biological parameters. One of the earliest
associations to be recognized was that between proteins and substances
of relatively small size, including steroid hormones. These protein-
steroid interactions occur in the circulating blood, at cellular surfaces,
in the substructures of the cells, and at the enzymic level. Obviously, the
ecology of the interaction and the nature of the protein and the steroid
involved are but a few determining factors in the overall physiological
effects and in the physicochemical parameters at this interaction. The
association of steroids with plasma proteins is the subject of the present
paper. Even though it is customary to think of the interaction between
plasma proteins and steroids as a means of transporting these hormones,
it will be shown later in the paper that the protein-steroid moiety of the
blood may serve more as a reservoir of the steroid, as a protector of the
steroid from catabolism, and as a buffer against inundation of the extra-
vascular spaces by the steroid hormone than as a mere transport agent.
Since the major field of biological activity of the steroid hormones re-
sides outside of their sites of synthesis, the nature of the physicochemical
state of steroids in the blood and their means of transport to their target
organs have been of considerable interest to those engaged in the study
of various facets of endocrinology. The steroid hormones are transported
primarily via the blood. The relatively low solubility of steroids in aque-
ous media, which is increased by the presence of albumin, made the
* Supported in part by Grants AM-01240 and CA-03359 from the United States Public
Health Service.
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