Regulation of Aldosterone Biosynthesis: Physiological and Clinical Aspects

374 Pages·1988·14.051 MB·English

by  Prof. Dr. med. Jürg Müller (auth.)

Monographs on Endocrinology
Volume 29
Edited by
F. Gross (t), Heidelberg· M. M. Grumbach, San Francisco
A. Labhart, Zurich· M. B. Lipsett (t), Bethesda
T. Mann, Cambridge· L. T. Samuels (t), Salt Lake City
J.Zander, Munchen
Jurg Muller
Regulation
of Aldosterone
Biosynthesis
Physiological
and Clinical Aspects
With 55 Figures and 13 Tables
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Prof. Dr. med. Jiirg Miiller
Steroid Laboratory,
Dept. of Medicine, University Hospital
CH- 8091 Zurich/Switzerland
This volume is the second, revised edition of Vol. 5 published
within the same series
ISBN-13:978-3-642-83122-5 e-ISBN-13:978-3-642-83120-1
DOl: 10.1007/978-3-642-83120-1
Library of Congress Cataloging-in-Publication Data
Miiller, Jiirg, 1931-
Regulation of aldosterone biosynthesis 1 Jiirg Miiller. - 2nd rev. ed.
p. cm. - (Monographs on endocrinology; v. 29)
Bibliography: p. Includes index.
ISBN-13:978-3-642-83122-5(U. S.)
1. Aldosterone - Synthesis - Regulation. I. Title. II. Series.
[DNLM: 1. Aldosterone - biosynthesis. W1 M057 v. 291 WK 755 M958r]
QP188.A28M84 1988 599'.01927 - dc 19
DNLM/DLC 87-28520 for Library of Congress CIP
This work is subject to copyright. All rights are reserved, whether the whole or part
of the material is concerned, specifically the rights of translation, reprinting, reuse of
illustrations, recitation, broadcasting, reproduction on microfilms or in other ways,
and storage in data banks. Duplication of this publication or parts thereof is only
permitted under the provisions of the German Copyright Law of September 9, 1965,
in its version of June 24, 1985, and a copyright fee must always be paid. Violations
fall under the prosecution act of the German Copyright Law.
© Springer-Verlag Berlin, Heidelberg 1988
Solicover reprint of the hardcover 2nd edition 1988
The use of registered names, trademarks, etc. in this publication does not imply, even
in the absence of a specific statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
Product Liability: The publisher can give no guarantee for information about drug
dosage and application thereof contained in this book. In every individual case the
respective user must check its accuracy by consulting other pharmaceutical literature.
Typesetting: Georg Appl, Wemding.
2127/3020-543210
To John P. Coghlan
in friendship and admiration
Preface to the Second Edition
Sixteen years is a long time, not only in human life but also in the rapid history
of contemporary endocrinology. Since the publication of the first edition of this
monograph, numerous new lines of research and discoveries have greatly contrib
uted to our knowledge of the physiological and pathological regulation of aldos
terone biosynthesis in man and animals. The first reports about a sensitive ra
dioimmunoassay for plasma aldosterone and about a preparation of dispersed
zona glomerulosa cells were published in 1970 (Mayes et al. 1970; Haning et al.
1970). These two developments alone turned out to have a tremendous impact on
research in aldosterone physiology (for reviews see Coghlan et al. 1979b; J. F. Tait
et al. 1980b). In 1971, atrial natriuretic peptides, somatostatin, and the precursor
molecule of ACTH had not yet been discovered. Angiotensin antagonists and con
verting-enzyme inhibitors were not yet available. The clinical syndrome of hypo
reninemic hypo aldosteronism was unknown. The possible roles of prostaglandins
and dopamine in the control of aldosterone pwduction had not been considered.
Cyclic AMP was then the only substance with a clearly established second-mes
senger function.
The following is an attempt to update the first edition of this monograph by
including the most important developments since 1971, but without altering the
basic concept and general structure of the book. It is still a heavily biased, one
man's overview of a vast, complex, and rapidly growing area of physiological
research. Although the volume of the text and the number of references have been
substantially increased, the revised monograph is far from being complete. It is
intended to be a road map rather than an encyclopedia.
Zurich, September 1987 Jurg Muller
VIII Acknowledgements
Acknowledgements
This book is dedicated to John P. Coghlan, Melbourne, whose own research has
greatly contributed to our knowledge of the physiological regulation of aldoster
one biosynthesis and who has been to me a constant source of inspiration and
encouragement since 1959, when we met in the laboratory of Dr. Ralph E. Peter
son. In the winter (or rather Australian summer) of 1973174, I had the privilege of
working at the Howard Florey Institute of Experimental Physiology and Medi
cine. Many ideas expressed in this book are based on extensive discussions I had
then and thereafter with John Coghlan and his colleagues, among them Bruce
Scoggins, John McDougall, Marelyn Wintour, and Derek Denton.
All my own research cited in this review has been carried out in the Steroid
Laboratory, Metabolic Unit, Department of Medicine, University Hospital of
Zurich. It has been generously and continuously supported by the Government of
the Canton of Zurich, with substantial contributions under Research Grants 2579,
3853, 4742.3, 3.325.70, 3.018.73, 3.704-0.76, 3.804-0.79, 3.929-0.82, and 3.882-0.85
from the Swiss National Foundation for Scientific Research. I am most grateful
for the outstanding contributions made by my inspired, imaginative, and hard
working research assistants Klaus Baumann, Bernhard Trost, Jan Komor, Philippe
Haldy, Conradin Meuli, and Markus Lauber and for the excellent technical assis
tance by Daniella Vogelsang, Catharina Modeer, Gisela Mohren, Lotti Berchtold,
Elsbeth Lauffer, Margrit Wellauer, Lilian Frei, Athena Reichardt, Idda Rutz, Bir
git Hauri, Eva-Grethe Lund, Lilian Hofstetter, Patricia Canlas, Heidi Seiler, Cor
nelia Henzi, Carmen Matt, and Sonia Maggetti. Some of the studies were per
formed in collaboration with Dr. W.Joe Weick, Dr. Walter H.Ziegler, Dr. Rolf
Huber, the late Prof. Franz Gross, Dr. Urs Hunziker, and Dr. Dorette B. Brunner.
Sincere thanks for timeless support and for giving a wide berth to my always com
plex but often unsuccessful research ventures are due to my past and present
superiors Prof. E. R. Froesch, Prof. A. Labhart, the late Prof. P. H. Rossier, and
Prof. P. Frick. I am still very much indebted to Dr. Ralph E. Peterson, who initi
ated my investigations on the regulation of aldosterone biosynthesis and who was
my major teacher in steroid biochemistry. This edition of the monograph would
h~lVe never been completed without the untiring efforts, patience, and proficiency
of Mrs. Rosmarie Meister and Mrs. Martha Salman, two of the best secretaries I
have had the pleasure to work with. I am also grateful for the skillful professional
work of Mr. I. Glitsch (artist) and Mr. S.Bernasconi (photography). The construc
tive critical advice given by Dr. Alessandro Capponi and his valuable help in edit
ing Sects. 4.1.5, 4.3, and 4.14 are much appreciated.
Jurg Muller
Preface to the First Edition
Most of our knowledge of the physiological control of aldosterone secretion is
based on animal experiments and clinical studies which were carried out in the
1950s and early 1960s by a large number of inspired, ingenious, and meticulous
researchers. Their work has been excellently reviewed by - among others -
A. F. Muller (1963), Blair-West et al. (1963), Laragh and Kelly (1964), Ganong et al.
(1966), Mulrow (1966), J. O. Davis (1967), and Gross (1967). According to the
majority of these investigators, aldosterone secretion is primarily regulated by the
renin-angiotensin system, with plasma sodium and potassium levels and pituitary
secretion of ACTH playing important secondary roles. During the past 6 years,
this hypothesis has been generally accepted and only occasionally challenged.
The following is an attempt to take - from the perspective of a relatively simple
in vitro model - a new look at the efferent axis of an apparently very complex
control system maintaining adequate aldosterone production in the mammalian
organism. My views are based mainly on a series of experiments which I have per
formed in order to study more closely the interactions of adrenocortical tissue
with substances capable of directly influencing aldosterone biosynthesis. Since all
these studies were carried out in vitro and with rat adrenal tissue only, the infor
mation obtained by means of this particular experimental model will be collated
with the findings of other investigators who have used a different experimental
approach to the study of aldosterone biosynthesis and its regulation in the rat as
well as in other animal species and in man.
Contents
1 Zona Glomerulosa of the Adrenal Cortex: Source of Aldosterone. . . .. 1
2 Pathway of Aldosterone Biosynthesis ..... 5
2.1 Classical Pathway and Alternative Pathways. 5
2.2 Corticosterone as an Intermediate Product. . . . . . . . . . . 6
2.3 18-Hydroxycorticosterone: Intermediate Product or By-product? . . . 8
2.4 Alternative Pathway Through 18-Hydroxy-11-deoxycorticosterone? .. 12
2.5 Deoxycorticosterone Secretion . . . . . . . . . 14
3 Aldosterone Biosynthesis by Cell-Free Systems . 16
4 Substances Directly Influencing Aldosterone Biosynthesis in Short-term
Incubation or Perfusion Experiments ............ . . . .. 22
4.1 Angiotensins . . . . . . . . 22
4.1.1 Angiotensin II ... 22
4.1.2 Angiotensin III . . . 27
4.1.3 Angiotensin I and Des-aspl-angiotensin I 30
4.1.4 Synthetic Angiotensin Analogues . . . 30
4.1.5 Adrenocortical Angiotensin Receptors .. 32
4.2 Monovalent Cations . . . . . . . 34
4.2.1 Sodium . . . . . . . . . . . . . . . . 34
4.2.2 Potassium.................... 37
4.2.3 Ammonium, Rubidium, and Cesium . . . . . 41
4.2.4 Lithium . . . . 43
4.2.5 Hydrogen Ions . 43
4.3 Divalent Cations . . . . 44
4.3.1 Calcium....... . . . . . . . . . . . 44
4.3.2 Substances Affecting Transport and Second-Messenger
Functions of Calcium ................ . . . 46
4.3.3 Magnesium............................ 49
4.4 ACTH, ACTH-related Peptides, and Other Pituitary Hormones. . . 49
4.4.1 ACTH........................ . . . . .. 49
4.4.2 ACTH-related Pituitary Peptides . . . . . . . . . . . . . .. 53
4.4.3 Prolactin....................... . . . . .. 57
XII Contents
4.4.4 Aldosterone-Stimulating Factor . . . . . . . . . . . . . . . . 57
4.4.5 Vasopressin..................... ...... 58
4.5 Amines ...................... . 59
4.5.1 Serotonin . . . . . . . . . . . . . . . . . . . . . . 59
4.5.2 Serotonin-Related Indole Derivatives. . . . . . . 62
4.5.3 Serotonin Antagonists . . . . . . . . . . . . . . . . . . . . . . .. 63
4.5.4 Dopamine, Dopaminergic Agonists, and Dopamine Antagonists 64
4.5.5 Histamine and Histamine Antagonists . . . . . . . . . . . . . 67
4.5.6 Adrenergic Agonists and Antagonists. . . . . . . . . . 67
4.6 Prostaglandins and Inhibitors of Prostaglandin Biosynthesis . . . . . 68
4.6.1 Prostaglandins .............. 68
4.6.2 Inhibitors of Prostaglandin Biosynthesis . 70
4.7 Aldosterone-Inhibiting Peptides ........ 71
4.7.1 Atrial Natriuretic Peptides . . . . . . . . . . . 71
4.7.2 Adrenal-Medullary Inhibitory Factor. . . . . 75
4.7.3 Somatostatin ... . . . . . . . . . . . . 75
4.8 Specific Inhibitors of Steroidogenic Enzymes . . . . 76
4.8.1 Metyrapone..................... ..... 76
4.8.2 Su-8000, Su-9055, and Su-10603 .................. 77
4.8.3 Aminoglutethimide........... . . . . . . . . . 79
4.8.4 Cyanosteroids........... 79
4.8.5 Spirolactones........... 80
4.9 Inhibitors of RNA or Protein Synthesis 81
4.9.1 Actinomycin D . . . . . . . . . . . 81
4.9.2 Cycloheximide . . . . . . . . . . . 82
4.9.3 Puromycin and Chloramphenicol. 84
4.10 Steroid Hormones . . . . . . . . . . . 85
4.10.1 Corticosteroids and Gestagens . 85
4.10.2 Androgens and Estrogens . . . . 86
4.11 Ouabain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
4.12 Miscellaneous Biological Substances with Direct Stimulatory or
Inhibitory Effects on Aldosterone Biosynthesis . . . . . . . . . . 89
4.13 Site of Action of Stimulators or Inhibitors in the Biosynthetic Pathway. 90
4.13.1 "Early Steps" and "Late Steps" .. ..... 90
4.13.2 Endogenous Steroid Output. . . . . . . 91
4.13.3 Conversion of Labeled Precursors ...... 92
4.13.4 Experiments with Unlabeled Precursors . . . 94
4.13.5 Experiments with Inhibitors of Steroidogenic Enzymes. 95
4.14 Primary Effects and Intracellular Mediation. . . . . . . . . . . . 96
4.14.1 General Considerations . . . . . . . . . . . . . . . . . . . . . .. 96
4.14.2 Cyclic AMP. . . . . . 97
4.14.3 Cyclic GMP .............................. 100
Contents XIII
4.14.4 Calcium .................... . · 101
4.14.5 Phospholipid Metabolism .......... . .104
4.14.6 Intracellular Potassium and (Na, K)-ATPase · 106
5 Alterations in Aldosterone Biosynthesis and Secretion in Long-Term
Experiments and Diseases . . . . . . . . . . . . . . . . 108
5.1 Alterations in Sodium Intake or in Sodium Balance. . 108
5.1.1 "Sodium Deficiency" ............. . · 108
5.1.2 Morphological and Histochemical Changes . · 109
5.1.3 Altered Sensitivity of the Zona Glomerulosa to
Aldosterone-Stimulating Substances . . . . · 110
5.1.4 Sites of Action in the Biosynthetic Pathway · 112
5.1.5 Role of the Renin-Angiotensin System .. · 117
5.1.6 Role of Plasma Potassium Concentration · 120
5.1.7 Role of Plasma Volume ......... . · 120
5.1.8 Role of Plasma Sodium Concentration .. · 124
5.1.9 Involvement of the Central Nervous System. · 125
5.2 Alterations in Potassium Intake or in Potassium Balance . . 126
5.2.1 General Considerations . . . . . . . . . . . . . 126
5.2.2 Morphological Changes . . . . . . . . . . . . . 127
5.2.3 Duration of Stimulatory Effects of Potassium . 127
5.2.4 Alterations in Zona Glomerulosa Sensitivity . . 128
5.2.5 Site of Action in the Biosynthetic Pathway . . . 129
5.2.6 Potassium-Induced Mitochondrial Protein. . . 133
5.2.7 Potassium Intake and the Renin-Angiotensin System . . 133
5.3 Exogenous Angiotensin or Renin. . . . . . . . . . . . . . . . . 136
5.3.1 Aldosterone Stimulation by Pressor and Nonpressor Doses . 137
5.3.2 Selectivity of Aldosterone Stimulation . . . . . . . . . . . . 138
5.3.3 Persistence of Aldosterone Stimulation. . . . . . . . . . . . 140
5.3.4 Effects on Angiotensin II Receptors and on Steroidogenic
Enzymes. . . . . . . . . . . . . . . . . . . . 142
5.3.5 Effects on Sodium Balance ....... . . . . 143
5.3.6 Renal Arterial Infusion of Angiotensin II .. . 144
5.3.7 Immunization Against Renin or Angiotensin . 144
5.3.8 Morphological and Histochemical Alterations of the Adrenal
Cortex. . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
5.4 Pharmacological Blockade of the Renin-Angiotensin System . 146
5.4.1 Angiotensin Antagonists. . . . . . . 146
5.4.2 Converting-Enzyme Inhibitors .... . 148
5.4.3 Beta-Adrenergic Blocking Agents . . . . 153
5.4.4 Inhibitors of Prostaglandin Synthesis. . 155
5.5 Role of the Kidneys . . . . . . . . . . . . . . . 157
5.5.1 Renovascular Hypertension . . . . . . . 157
5.5.2 Renal Denervation, Kidney Transplantation, and Unilateral
Nephrectomy ........................ " . 163