Hormonal Steroids Biochemistry, Pharmacology, and Therapeutics. Proceedings of the First International Congress on Hormonal Steroids

555 Pages·1964·13.468 MB·English

by  L. Martini (Eds.)

HORMONAL STEROIDS
Biochemistry, Pharmacology,
and Therapeutics
PROCEEDINGS OF THE FIRST INTERNATIONAL
CONGRESS ON HORMONAL STEROIDS
Edited by
L. MARTINI AND A. PECILE
Department of Pharmacology
University of Milan
Milan, Italy
VOLUME 1
1964
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Library of Congress Catalog Card Number: 64-23201
Printed in Hungary
Contributors to Volume i
Numbers in parentheses indicate the pages on which the authors' contributions begin
R. ABRAMS, Department of Physiology, School of Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania, U.S.A. (p. 251).
L. ADEZATI, Clinica Medica, University of Genoa, Italy (p. 317).
I. ASSENMACHER, L·aboratoire de Physiologie Animale, Faculte des Sciences,
Montpellier, France (p. 273).
E. ALPERT, Merck Sharp and Dohme Research Laboratories, West Point,
Pennsylvania, U.S.A. (p. 517).
L. BASCHIERI, Istituto Patologia Medica, University of Rome, Rome, Italy
(p. 533).
G. K. BENSON, Department of Veterinary Anatomy, The University, Liver-
pool, England (p. 247).
P. M. F. BISHOP, Institute of Obstetrics and Gynecology, London, England
(p. 65).
W. P. BLACK, Boston City and Lying In Hospitals, Harvard Medical School,
Boston, Massachusetts, U.S.A. (p. 81).
I. L. BONTA, Department of Pharmacological Research, N. V. Organon, Oss,
The Netherlands (p. 493).
A. BOWERS, Research Laboratories, Syntex, S. A., Mexico City, Mexico
(p. 29).
R. V. BROOKS, Department of Medicine and Chemical Pathology, St.
Thomas's Hospital Medical School, London, England (p. 441).
I. E. BUSH, Department of Physiology, The Medical School, Birmingham,
England (p. 353).
J. CAHN, Labor atoire de Neurochimie, CUnique Neurochirurgieale, Paris,
France (p. 501).
H. J. CAMPBELL, Department of Neuroendocrinology, Institute of Psy-
chiatry, The Maudsley Hospital, London, England (p. 259).
A. CARNI CELLI, Istituto di Patologia Medica, University of Pisa, Pisa,
Italy (p. 167).
F. CERESA, Clinica Medica, University of Turin, Turin, Italy (p. 99).
J. J. CHART, Research Department, Ciba Pharmaceutical Company, Summit,
New Jersey, U.S.A. (p. 399).
B. T. DONOVAN, Department of Neuroendocrinology, Institute of Psychiatry,
The Maudsley Hospital, London, England (p. 231).
R. I. DORFMAN, Worcester Foundation for Experimental Biology, Shrews-
bury, Massachusetts, U.S.A. (p. 39).
F. J. EBLING, Department of Zoology, Sheffield University, Sheffield, England
(p. 537).
vi
R. H. EGDAHL, Strauss Surgical Kesearch Laboratory, Medical College of
Virginia, Richmond, Virginia, U.S.A. (p. 209).
J. EICHHORN, The Worcester Foundation for Experimental Biology, Shrews-
bury, Massachusetts, U.S.A. (p. 359).
E. EISENBERG, The Department of Medicine, University of California School
of Medicine, San Francisco, California, U.S.A. (p. 517).
L. L. ENGEL, The John Collins Warren Laboratories of the Huntingdon
Memorial Hospital of Harvard University, Massachusetts General
Hospital, Boston, Massachusetts, U.S.A. (p. 291).
A. ERCOLI, Vister Kesearch Laboratories, Casatenovo (Como), Italy.
J. W. EVERETT, Department of Anatomy, Duke University School of Medicine,
Durham, North Carolina, U.S.A. (p. 235).
G. FALUDI, Associate in Medicine, Department of Medicine, Hahnemann
Medical College General Hospital, Philadelphia, Pennsylvania, U. S. A.
(p. 515).
G.FARRELL, Department of Physiology, Western KeserveUniversity, Cleveland,
Ohio, U.S.A. (p. 141).
G. FEKETE, Chemical Works of Gedeon Kichter, Ltd., Budapest, Hungary
(p. 351).
W. H. FISHMAN, Tuft University School of Medicine, Boston, Massachusetts,
U.S.A. (p. 301).
B. FLERKO, Department of Anatomy, Medical University, Pecs, Hungary
(p. 221).
V. FORMISANO, Arnold Biological Laboratory, Brown University, Providence,
Khode Island, U.S.A. (p. 559).
T. F. GALLAGHER, Sloan-Kettering Institute for Cancer Kesearch, 410 East
68 Street, New York, New York, U.S.A. (p. 103).
E. M. GLENN, Kesearch Laboratories, The Upjohn Company, Kalama^po,
Michigan, U.S.A. (p. 319).
S. GORDAN, The Department of Medicine, University of California School of
Medicine, San Francisco, California, US.A. (p. 517).
J. K. GRANT, Department of Steroid Biochemistry, University of Glasgow,
Scotland (p. 137).
R. B. GREENBLATT, Department of Endocrinology, Medical College of
Georgia, Augusta, Georgia, U.S.A. (p. 397).
F. GROSS, Research Laboratories of the Pharmaceutical Department ofCIBA
Limited, Basel, Switzerland (p. 153).
M. GUT, Worcester Foundation for Experimental Biology, Shrewsbury,
Massachusetts, U.S.A. (p. 81).
I. D. K. HALKERSTON, The Worcester Foundation for Experimental
Biology, Shrewsbury, Massachusetts, U.S.A. (p. 359).
O. HECHTER, The Worcester Foundation for Experimental Biology, Shrews-
bury, Massachusetts, U.S.A. (p. 359).
J. HILLIARD, Department of Anatomy, University of California, Los
Angeles, California, U.S.A. (p. 263).
vii
J. HOLSINGER, Department of Anatomy, Duke University School of Medicine,
Durham, North Carolina, U.S.A. (p. 235).
D. M. HUME, Lewis L. Strauss Surgical Research Laboratory, Department
of Surgery, Medical College of Virginia, Richmond, Virginia, U.S.A.
(p. 185).
J. JACQUES, College deFrance, Laboratoire de Chimie Organique des Hormones,
Paris Ve, France (p. 3).
E. JOHNSON, Department of Zoology, University of Reading, Surrey, England
(p. 569).
C. M. KAGAWA, Division of Biological Research, G. D. Searle and Company
Chicago, Illinois, U.S.A. (p. 445).
A. M. KLIGMAN, Duhring Laboratories, University of Pennsylvania, Phila-
delphia, Pennsylvania, U.S.A. (p. 559).
A. KLOPPER, Obstetric Medicine Research Unit, Medical Research Council,
Aberdeen, Scotland (p. 413).
D. S. LAYNE, Worcester Foundation for Experimental Biology, Shrewsbury,
Massachusetts, U.S.A. (p. 433).
L. J. LERNER, Squibb Institute for Medical Research, New Brunswick, New
Jersey, U.S.A. (p. 523).
T. F. LEVEQUE, Department of Anatomy, University of Maryland Medical
School, Baltimore, Maryland, U.S.A. (p. 207).
B. LITTLE, Worcester Foundation for Experimental Biology, Shrewsbury,
Massachusetts, U.S.A. (p. 81)
S. M. MCCANN, Department of Physiology, School of Medicine, University
of Pennsylvania, Philadelphia, Pennsylvania, U.S.A. (p. 251).
W. M. MCISAAC, Department of Physiology, Western Reserve University,
Cleveland, Ohio, U.S.A. (p. 141).
V. B. MAHESH, Department of Endocrinology, Medical College of Georgia,
Augusta, Georgia, U.S.A. (p. 397).
V. MARESCOTTI, Istituto di Patologia Medica, University of Pisa, Pisa,
Italy (p. 167).
L. MARTINI, Department of Pharmacology, University of Milan, Milan,
Italy (p. 199).
A. MELI, Warner-Lambert Research Institute, Morris Plains, New Jersey,
U.S.A. (p. 25).
I. H. MILLS, Department of Medicine and Chemical Pathology, St. Thomas's
Hospital Medical School, London, England (p. 441).
T. MIYAKE, Shionogi Research Laboratory, Fukushima-ku, Osaka, Japan
(p. 51).
W. MONTAGNA, Arnold Biological Laboratory, Brown University, Providence,
Rhode Island, U.S.A. (p. 559).
Μ. MOTTA, Department of Pharmacology, University of Milan, Milan, Italy
(p. 199).
A. F. MÜLLER, Clinique Universitaire de Therapeutique, HSpital Cantonal
de Geneve, Geneve, Switzerland (p. 457).
viii
E. MÜLLER, Department of Pharmacology, University of Milan, Milan,
Italy (p. 199).
A. V. NALBANDOV, University of Illinois, Urbana, Illinois, US. A. (p. 283).
M. B. NIKITOVITCH-WINER, Department of Anatomy, University of
Kentucky College of Medicine, Lexington, Kentucky, US.A. (p. 217).
G. A. OVERBEEK, N. V. Organon, Oss, The Netherlands (pp. 37 and 493).
W. H. PEARLMAN, Department of Biological Chemistry, Harvard Medical
School, and Peter Bent Brigham Hospital, Boston, Massachusetts, U.S.A.
(p. 115).
G. PINCUS, Worcester Foundation for Experimental Biology, Shrewsbury,
Massachusetts, U.S.A. (p. 3).
H. M. RADFORD, Department of Anatomy, Duke University School of
Medicine, Durham, North Carolina, U.S.A. (p. 235).
D. RAMIREZ, Department of Physiology, School of Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania, U.S.A. (p. 251).
H. J. RINGOLD, Worcester Foundation for Experimental Biology, Shrews-
bury, Massachusetts, U.S.A. (p. 305).
A. RIONDEL, Boston City and lying in Hospitals, Harvard Medical School,
Boston, Massachusetts, U.S.A. (p. 81).
A. RIVERA, Metabolic Unit, Hospital de Enfermedades de la Nutricion,
Mexico, D. F. (p. 165).
R. ROMANELLI, lstttuto diPatologia Medica, University of Pisa, Italy (p. 149).
F. ROSEN, Roswell Park Memorial Institute, Buffalo, New York, U.S.A.
(p. 355).
S. ROY, Department of Endocrinology, Medical College of Georgia, Augusta,
Georgia, U.S.A. (p. 397).
M. SAFFRAN, Allan Memorial Institute, McGill University, Montreal,
Canada (p. 197).
G. SALA, Clinica Medica, University of Milan, and L·aboratori di Ricerche
Farmitalia, Milan, Italy (p. 67).
C. H. SAWYER, Department of Anatomy, University of California, Los
Angeles and Veterans Administration Hospital, Long Beach, California,
U.S.A. (p. 263).
H. F. L. SCHOLER, N. V. Philips-Duphar Research Laboratories Weesp,
The Netherlands (p. 53).
J. J. SCHNEIDER, Department of Medicine, Jefferson Medical College,
Philadelphia, Pennsylvania, U.S.A. (p. 127).
J. F. SCOTT, Department of Biological Chemistry and the Department of
Anatomy, Harvard Medical School, Boston, Massachusetts, U.S.A.
(p. 291).
H. SHEPPARD, Research Department, CUBA Pharmaceutical Company,
Summit, New Jersey, U.S.A. (p. 399).
F. SILVESTRINI, Clinica medica, University of Milan, Milan, Italy (p. 415).
R. S. SNELL, Department of Anatomy, The Medical School, King's College,
University of Durham, Newcastle upon Tyne, England (p. 553).
ix
B. G. STEINET^, Warner-Lambert Research Institute, Morris Plains, New
Jersey, U.S.A. (p. 25).
A. M. STOFFYN, Department of Biological Chemistry and the Department
of Anatomy, Harvard Medical School, Boston, Massachusetts, US.A.
(p. 291).
G. K. SUCHOWSKY, Laboratori Ricerche Farmitalia, Milan, Italy (p. 77).
J. F. TAIT, Worcester Foundation for Experimental Biology, Shrewsbury,
Massachusetts, U.S.A. (p. 81).
S. A. S. TAIT, Worcester Foundation for Experimental Biology, Shrewsbury,
Massachusetts, U.S.A. (p. 81).
R. D. TANZ, Department of Physiology, Western Reserve University, Cleve-
land, Ohio, U.S.A. (p. 525).
A. N. TAYLOR, Department of Physiology, Western Reserve University,
Cleveland, Ohio, U.S.A. (p. 141).
F. TRONCHETTI, Istituto di Patologia Medica, University of Pisa, Pisa,
Italy (p. 167).
W. W. TULLNER, Endocrinology Branch, National Cancer Institute,
Bethesda, Maryland, U.S.A. (p. 383).
J. T. VELARDO, Institute for the Study of Human Reproduction at the Saint
Ann Hospital, Grasselli Library, John Carrol University, University
Heights, Cleveland, Ohio, U.S.A. (p. 463).
A. VERMEULEN, Department of Endocrine and Metabolic Diseases, Medical
Clinic, State University, Ghent, Belgium (p. 111).
C. A. VILLEE, Department of Biological Chemistry, Harvard Medical
School, and the Research Laboratories of the Boston Lying In Hospital,
Boston, Massachusetts, U.S.A. (p. 375).
K. D. VOIGT, 2nd Medical University Clinic, Hormone Laboratory, Univer-
sity of Hamburg, Hamburg—Eppendorf, West Germany (p. 125).
A. WHITE, Department of Biochemistry, Albert Einstein College of Medicine,
Yeshiva University, New York, New York, U.S.A. (p. 571).
D. DE WIED, Department of Pharmacology, University of Groningen, Gronin-
gen, Holland (p. 181).
C. D. WITHROW, Department of Pharmacology, University of Utah College
of Medicine, Salt Lake City, Utah, U.S.A. (p. 503).
D. M. WOODBURY, Department of Pharmacology, University of Utah College
of Medicine, Salt Lake City, Utah, U.S.A. (p. 503).
A. ZAFFARONI, Research Laboratories, Syntex, S. A., Mexico City, Mexico
(p. 29).
Foreword
It is over thirty years since the isolation and chemical identification
of the first hormonal steroid (estrone). There followed in the 1930's
a brilliant series of investigations which led to the indentification of
most of the major steroids secreted by the ovaries, the testes, the adrenal
cortex, and the placenta. Since those days, when these steroids were
available at best in milligram amounts, there has been an exponential
increase in the amounts of steroid hormones preparable by partial
synthesis and in the investigation of their pharmacological, physiolo-
gical, and biochemical properties. Keeping pace with, and, indeed, often
anteceding our knowledge of the steroid hormones, has been the pro-
duction of derivatives, analogues, and homologues of the hormones.
In order to encompass the rich chemical, biochemical, and medical
knowledge in the steroid hormone field, the inclusion of work with
these steroid relatives led to the "International Congress on Hormonal
Steroids." Our knowledge of the regulatory activity of the steroid
hormones at the organ, tissue, and cellular levels has been aided and
enlarged by studies with the synthetics. Their contribution to the
sharpened insight is obvious in numerous papers presented to this
Congress, and included in this volume.
As we review the subject matter presented in the symposia and
round-table conferences, the major areas of research with steroids are
sharply illuminated. These major areas may be listed as:
(1) Steroid chemistry, ranging from the natural product isolation to
organic syntheses and including studies of reaction mechanisms.
(2) The biogenesis and metabolic transformations of the naturally
occurring hormones.
(3) The secretion, transport, conjugation, and excretion of the steroid
hormones and of synthetic chemical relatives.
(4) The control of steroid hormone secretion by endogenous humoral
and neurohumoral agents and by diverse exogenous agents.
(5) The relationship between chemical structure and physiological
function of hormonal steroids of all types.
(6) The regulatory effects of hormonal steroids on specific target tissues.
(7) The repercussive, secondary or indirect actions of the hormonal
steroids upon diverse processes.
(8) The role of hormonal steroids in endocrine and neuroendocrine
pathology, including steroid therapy.
(9) Hormonal adjustments to physical and psychological stresses
and to the aging process.
xi
xii
Among the papers presented to the Congress are accounts of data
extremely pertinent to the foregoing topics. These papers illustrate
the enormous amount of research activity devoted to the steroids and
their biological and medical involvements. Indeed, they confirm the
impression that there is scarcely a vital process, an aspect of behavior
or personality, or organic pathological lesion which is not in one way
or another affected by steroids. From the crowns of our heads to the
tips of our toes, the steroid flux is incessantly at work. In this volume,
the reader will find able presentations by experienced and sagacious
investigators of the what, how, and why of this multivarious steroid
activity.
We wish to thank all the people who have contributed to the organi-
zation of the Congress and to the publication of these volumes and
made them a successful reality: Drs. F. Fraschini, G. Gavazzi, G.
Giuliani, G. Mangili, M. Motta, E. Müller, L. Martini, and A. Pecile.
GREGORY PINCUS EMILIO TRABUCCHI
The Worcester Foundation Department of Pharmacology
for Experimental Biology University of Milan, Italy
Shrewsbury, Massachusetts
Contents of Volume 2
Recent Applications of Mass Spectrometry in Steroid Chemistry. By
C. Djerassi, H. Mudzikiewicz, and J. M. Wilson
Some Thermodynamic Factors in a Postulated Association of Hydro-
cortisone with a Complementary B-Face Receptor. By L. H.
Sarett
The Stereochemistry of Unsymmetrically Substituted 16a, 17a-Methyl-
ene-dioxyprogesterones. By J. Fried and E. F. Sabo
The Chemistry and Biology of 17-Substituted Estrene-3/J, 17/?-diols.
By F. B. Colton and P. Klimstra
Structure-Activity Relationships of Some Aldosterone Antagonists.
By R. R. Burtner
Synthesis of a Structural Isomer of Aldosterone and of Related
Compounds. By T. Kubota and M. Ehrenstein
Synthesis of 4-Hydroxy-3-Keto-id4-Steroids. By B. Camerino
7a-Methyltestosterones, A New Class of Potent Anabolic Agents.
By J. A. Campbell and J. C. Babcock
New Heterocyclic Compounds. By P. de Ruggieri and C. Gandolfi
Syntheses of a-Methyl Steroids. By R. Wiechert
Some Recent Advances in the Chemistry of 16-/?-Methylsteroids. By
G. Nathanson and E. Testa
Sterically Controlled Grignard Reactions: The Preparation of 17-
Methylated Progesterone Derivatives. By R. Deghenghli, Y.
Lefebvre, P. F. Morand, and R. Gaudry
New Reactions in Corticosteroid Side Chain. By R. Gardi
Intramolecular Condensation of Some 6-Acetylthio-Steroids. By K.
Takeda and T. Komeno
Anabolic and Androgenic Activities of 7a, 10a-Dimethyl-testosterone
(U-190763), A New Anabolic Steroid. By J. C. Stucki, G. W.
Duncan, and S. C. Lyster
Ring A Modified Androstanes. New Classes of Anabolic Agents. By
A. Bowers
Steroid-17/?-yl Acetals and Enol Ethers: New Orally Active, C-17a
not Alkylated, Anabolic Compounds. By G. Falconi
Recent Findings in Anabolic Steroids. By G. K. Suchowsky and
K. Junkman
Wy 3475, A New, Potent, Orally Active Anabolic Agent. By R. A.
Edgren and H. Smith
The Biological Evaluation of the Anabolic Activity. By G. Baldratti
Studies on the Dissociation between Androgenic and Myotropic
xvil