Mechanisms of Steroid Action

185 Pages·1981·18.64 MB·English

by  G. P. Lewis, M. Ginsburg (eds.)

MECHANISMS OF STEROID ACTION
Previously published volumes
1970 Aldridge: Mechanisms of Toxicity
1971 Rabin and Freedman: Effects of Drugs on Cellular Control Mechanisms
1972 Rang: Drug Receptors
1973 Callingham: Drugs and Transport Processes
1974 Parsons: Peptide Hormones
1975 Grahame-Smith: Drug Interactions
1976 Roberts: Drug Action at the Molecular Level
1977 Hughes: Centrally Acting Peptides
1978 Turk and Parker: Drugs and Immune Responsiveness
1980 Sandler: Enzyme Inhibitors as Drugs
1981 Birdsall: Drug Receptors and their Effectors
BIOLOGICAL COUNCIL
The Co-ordinating Committee for Symposia
on Drug Action
MECHANISMS OF
STEROID ACTION
Edited by
G. P. LEWIS
Institute of Basic Medical Sciences,
Royal College of Surgeons of England,
Lincoln's Inn Fields,
London
and M. GINSBURG
Department of P}larmacology,
Chelsea College,
University of London
M
© Institute of Biology Endowment Trust Fund 1981
Softcover reprint ofthe hardcover 1st edition 1981 978-0-333-32455-4
All rights reserved. No part of this publication may be reproduced or trans
mitted in any form or by any means, without permission
First published 1981 by
THE MACMILLAN PRESS LTD
London and Basingstoke
Associated companies in Delhi Dublin
Hong Kong Johannesburg Lagos Melboume
New York Singapore and Tokyo
Typeset by Reproduction Drawings Ltd. • Sutton, Surrey
ISBN 978-1-349-81347-6 ISBN 978-1-349-81345-2 (eBook)
DOI 10.1007/978-1-349-81345-2
Biological Council Co-ordinating Committee for Symposia on Drug Action
Report of a symposium held on 13 and 14 April 1981 in London
at the Imperial College of Science and Technology
Sponsored by:
Biochemical Society
British Association for Psychopharmacology
British Biophysical Society
British Pharmacological Society
British Society for Antimicrobial Chemotherapy
British Society for Immunology
The Physiological Society
The Royal Society of Medicine
Society of Chemical Industry Fine Chemicals Group
Society for Endocrinology
The organisers are grateful to the following for the generous financial support
which made the meeting possible:
The Wellcome Trust Reckitt and Colman Limited
Beecham Group Limited Roche Products Limited
The Boots Company Limited G. D. Searle and Company
Ciba-Geigy (UK) Limited Smith Kline & French Laboratories
Fisons Limited Limited
Glaxo (I 972) Charity Trust Smith and Nephew Research Limited
Imperical Chemical Industries Limited Syntex Pharmaceuticals Limited
Johnson & Johnson The Upjohn Company
Lilly Research Centre Limited Warner-Lam bert/Parke-Davis
Organised by a symposium committee consisting of:
G. P. Lewis (Chairman and Hon. Secretary)
R. J. Flower
M. Ginsburg
H.P. Rang
Symposium Contributors
N. Avogadri, P. Ferraboschi,
Department of Endocrinology, Department of Endocrinology,
University of Milano, University of Milano,
21 Via Andrea del Sarto, 21 Via Andrea del Sarto,
20129 Milano, Italy. 20129 Milano, Italy.
E-E. Baulieu,
R. J. Flower,
Laboratoire Hormones,
Department of Prostaglandin Research,
Inserm U 33, Faculte de Medecine,
Wellcome Research Laboratories,
942 70 Bicetre, France.
Langley Court, Beckenham, Kent
BR3 3BS, U.K.
P. A. Bell,
Tenovus Institute for Cancer Research,
Welsh National School of Medicine, M. Ginsburg,
Health Park, Cardiff CF4 4XX, Wales, Department of Pharmacology,
U.K. Chelsea College,
Manresa Road, London S. W. 3. U.K.
N. Birnbaumer,
Department of Cell Biology,
Baylor College of Medicine, G. L. Greene,
Houston, Texas 77030, U.S.A. Ben May Laboratory for Cancer Research,
The University of Chicago,
G. Blackwell, Chicago, Illinois 60637, U.S.A.
Department of Prostaglandin Research,
Wellcome Research Laboratories,
W. W.Grody,
Langley Court, Beckenham, Kent
Department of Cell Biology,
BR3 3BS, U.K.
Baylor College of Medicine,
Houston, Texas, 77030, U.S.A.
F. Celotti,
Department of Endocrinology,
University of Milano, E. V. Jensen,
21 Via Andrea del Sarto, Ben May Laboratory for Cancer Research,
20129, Milano, Italy. The University of Chicago,
Chicago, Illinois 60637, U.S.A.
C. R. Clark,
Department of Obstetrics & Gynaecology,
R. J. B. King,
Yale University School of Medicine,
Hormone Biochemistry Department,
333, Cedar Street,
Imperial Cancer Research Fund,
New Haven, Connecticut 06510, U.S.A.
Lincoln's Inn Fields, London
WC2A 3PX, U.K.
M. DiRosa,
University degli Studi di Napoli, F. Labrie,
Istituto di Farmacologia Sperimentale, Department of Molecular Endocrinology,
Via Leopolda Rodino 22, Le Centre Hospitalier de I'Universite
80138 Naples, Italy. Laval, Quebec GIV 4G2, Canada.
vii
B. S. McEwen, J.P. Raynaud,
The Rockefeller University, New York, Roussel-Uclaf,
New York, 10021, U.S.A. 75007 Paris, France.
N.J. MacLusky, J. M. Renoir,
Department of Obstetrics & Gynaecology, Laboratoire Hormones,
Yale University School of Medicine, Inserm U33, Faculte de Medecine,
333, Cedar Street, 94270 Bicetre, France.
New Haven, Connecticut 06510, U.S.A.
W. T. Schrader,
L. Martini, Department of Cell Biology,
Department of Endocrinology, Baylor College of Medicine,
University of Milano, Houston, Texas 77030, U.S.A.
21 Via Andrea del Sarto,
20129, Milano, Italy. S. R. Slater,
Bioscience Department,
J. Mester, Imperial Chemical Industries,
Laboratoire Hormones, Pharmaceuticals Division,
Inserm U33, Faculte de Medecine, Alderley Park, Macclesfield,
942 70 Bicetre, France. Cheshire, U.K.
P. P. Minghetti, S. Tsurufuji,
Department of Cell Biology, Department of Biochemistry,
Baylor College of Medicine, Faculty of Pharmaceutical Sciences,
Houston, Texas 77030, U.S.A. Tokohu University,
Aoba, Aramaki, Sendai 980, Japan.
M. Motta,
Department of Endocrinology, A. E. Wakeling,
University of Milano, Bioscience Department,
21 Via Andrea del Sarto, Imperial Chemical Industries,
20129 Milano, Italy. Pharmaceuticals Division,
Alderley Park, Macclesfield,
F. N aftolin, Cheshire, U. K.
Department of Obstetrics & Gynaecology,
Yale University School of Medicine, N. L. Weigel,
33 3, Cedar Street, Department of Cell Biology,
New Haven, Connecticut 06510, U.S.A. Baylor College of Medicine,
Houston, Texas 77030, U.S.A.
T. Ojasoo,
Roussel - Uclaf, A. Wolfson,
75007 Paris, France. Laboratoire Hormones,
Inserm U 331, Faculte de Medecine,
B. W. O'Malley, 94270 Bicetre, France.
Department of Cell Biology,
Baylor College of Medicine, C-R. Yang,
Houston, Texas 77030, U.S.A. Laboratoire Hormones,
Inserm U 33, Faculte de Medecine,
C. M. Paden, 942 70 Bicetre, France.
Rockefeller University,
1230 York Avenue,
New York, New York 10021, U.S.A.
L. Parente,
Universita degli Studi di Napoli,
Istituto di Farmacologia Sperimentale,
Via Leopolda Rodino 22,
80138 Naples, Italy.
viii
Contents
Sponsoring societies v
Bodies from whom financial support was received v
Symposium contributors vii
1. Anti-oestrophilin antibodies as probes for receptor structure and
function. E. V. Jensen and G. L. Greene
2. Characterization of the 'native' and 'activated' progesterone and
oestrogen receptors from chick oviduct cytosol. J. Mester, J. -M. Renoir,
C. -R. Yang, A. Wolfson and E. -E. Baulieu 15
3. The structure and function of the progesterone receptor. M. Birnbaumer,
N. L. Weigel, P. P. Minghetti, W. W. Grody, W. T. Schrader and
B. W. O'Malley 29
4. Effects of female sex hormones on human endometrium in relation to
neoplasia. R. J. B. King 49
5. Steroid hormones: blood-borne modulators of nerve cell structure
and activity. B.S. McEwen 59
6. Steroids and the cells of the immune system. P. A. Bell 75
7. Molecular mechanisms and mode of action of anti-inflammatory
steroids. S. Tsurufuji 85
8. Mechanism of steroid induced inhibition of arachidonate oxidation.
R. J. Flower, G. J. Blackwell, M. DiRosa and L. Parente 97
9. End-organ metabolism of oestrogens. N.J. MacLusky, C. R. Clark,
C. M. Paden and F. Naftolin 115
10. Control of androgen metabolism in the peripheral and central
structures: physiological implications. L. Martini, N. Avogadri,
P. Ferraboschi, F. Ce1otti and M. Motta 133
11. Steroid hormones-agonists and antagonists. J.P. Raynaud, T. Ojasso
and F. Labrie 145
12. Biochemical and biological aspects of anti-oestrogen action.
A. E. Wakeling and S. L. Slater 159
Summing up. M Ginsburg 173
Index 177
ix
1
Anti-oestrophilin antibodies as probes
for receptor structure and function
Elwood V. Jensen and Geoffrey L. Greene (Ben May Laboratory for Cancer
Research, The University of Chicago, Chicago, Illinois 60637 USA)
INTRODUCTION
The original discovery of steroid hormone receptors (Glascock and Hoekstra,
1959; Jensen and Jacobson, 1960) and essentially all our understanding of
hormone-receptor interaction in responsive tissues (Jensen and DeSombre,
1973; Gorski and Gannon, 1976; O'Malley and Schrader, 1976) have depended
on experiments in which a radio1abelled hormone serves as a marker for the
receptor protein to which it binds. This ligand-binding approach has proved
useful in detecting and measuring receptor substances as well as for following
the receptor through purification procedures or during its biochemical inter-
action within the target cell. But despite the wealth of information they have
furnished during the past 20 years, ligand-binding procedures suffer from certain
limitations. Although strong, the association of hormone with receptor is non-
covalent, so the bound steroid is subject to displacement during experimental
manipulation of receptor preparations. Furthermore, the receptor proteins are
labile substances that irreversibly lose their ability to bind hormone by partial
denaturation or by the action of factors present in extracts of many tissues
and tumours. Unless some kind of exchange assay is carried out, which usually
requires warming, the labelled steroid fails to detect receptor that is already
occupied by endogenous hormone. It may also fail to recognise receptor in its
early stages of synthesis before it has acquired the ability to bind hormone or
in the later stages of its action where the steroid and receptor may have parted
company. Thus, there has been need for a means of detecting receptor proteins
that does not depend on the binding of labelled steroid and that will recognise