The Pituitary and Testis: Clinical and Experimental Studies

196 Pages·1983·8.319 MB·English

by  H. G. Burger, V. W. K. Lee (auth.), David M. de Kretser, Henry G. Burger, Bryan Hudson (eds.)

Monographs on Endocrinology
Volume 25
Edited by
F. Gross, Heidelberg· M.M. Grumbach, San Francisco
A. Labhart, Zurich . M.B. Lipsett, Bethesda
T. Mann, Cambridge . L.T. Samuels (t), Salt Lake City
J. Zander, Munchen
The Pituitary
and Testis
Clinical and Experimental Studies
Edited by
D.M. de Kretser, H.G. Burger, B. Hudson
With 92 Figures and 17 Tables
Springer-Verlag
Berlin Heidelberg New York Tokyo
1983
David M. de Kretser
Department of Anatomy, Monash University
Clayton, Victoria 31681 Australia
Henry G. Burger
Medical Research Center, Prince Henry's Hospital
St. Kilda Road, Melbourne, Victoria 30041 Australia
Bryan Hudson
Howard Florey Institute of Experimental
Physiology and Medicine, University of Melbourne
Parkville, Victoria 30521 Australia
ISBN-13:978-3-642-81914-8 e-ISBN-13 :978-3-642-81912-4
DOl: 10.1007/978-3-642-81912-4
Library of Congress Cataloging in Publication Data
Main entry under title: The pituitary and testis.
(Monographs on endocrinology; v. 25)
Includes bibliographical references and index.
Contents: Patterns of secretion and metabolism of the gonadotrophic hormones - Control of
FSH and LH secretion - Pituitary testicular axis during pubertal development - Changes in the
pituitary-testicular axis with age -[etc.]
1. Pituitary hormones. 2. Testis. I. De Kretser, David. II. Burger, Henry. III. Hudson, Bryan.
IV. Series. [DNLM: 1. Pituitary gland - PhysiOlogy. 2. Testis -PhysiOlogy.
WI M057 v. 25 1 WK 502 P962]
QP 572.P52P57 1983 612'.492 82-19185
ISBN-I3:978-3-642-81914-8 (U.S.)
This work is subject to copyright. All rights are reserved, whether the whole or part of the ma
terial is concerned, specifically those of translation, reprinting, re-use of illustrations, broad
casting, reproduction by photocopying machine or similar means, and storage in data banks.
Under § 54 of the German Copyright Law where copies are made for other than private
use, a fee is payable to 'Verwertungsgesellschaft Wort', Munich.
iEJ Springer-Verlag Berlin, Heidelberg 1983
Softcover reprint of the hardcover 1st edition 1983
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.
2127/3020-543210
List of Contributors
H.W.G. Baker, Howard Florey Institute of Experimental Physiology and
Medicine, Melbourne, Australia
W.J. Bremner, Division of Endocrinology and Metabolism, Veterans
Administration Medical Centre, Seattle, Washington, U.S.A.
H.G. Burger, Medical Research Centre, Prince Henry's Hospital,
Melbourne, Australia
Y.M. Hodgson, Department of Anatomy, Monash University, Melbourne,
Australia
B. Hudson, Howard Florey Institute of Experimental Physiology and
Medicine, Melbourne, Australia
J.B. Kerr, Department of Anatomy, Monash University, Melbourne,
Australia
D.M. de Kretser, Department of Anatomy, Monash University, Melbourne,
Australia
V.W.K. Lee, Medical Research Centre, Prince Henry's Hospital,
Melbourne, Australia
K.A. Rich, Department of Anatomy, Monash University, Melbourne,
Australia
Preface
This monograph brings together our work concerning the relationships be
tween the hypothalamus, pituitary and testis. The studies span approximate
ly a decade of collaborative work. Over this period our contributions and
those of many others have advanced greatly our understanding of many
aspects of male reproductive biology. This monograph attempts to survey
these developments and to highlight many unresolved issues. It also provides
an opportunity to demonstrate the value of investigations which relate bio
chemical to structural parameters and to illustrate the importance of animal
studies in elucidating biological principles with clinical applications. The
reverse is also important since the pathophysiology of human disorders of
ten provides insight into hitherto unsuspected basic mechanisms.
In any rapidly expanding field it is difficult to stop revising and extending
a manuscript. It is equally difficult to quote every reference in the field but
we trust that those of significance have not been omitted. Some of our
former students have collaborated with us as co-authors in producing this
monograph. It is equally important to recognise the contributions of our
other former students and colleagues who have physically participated in
the studies and without whose intellectual contributions a number of
concepts would not have been elucidated. Their work is acknowledged in
the text of the monograph and the extensive list of references.
David de Kretser
Henry Burger
Bryan Hudson
Acknowledgements
In reviewing the contributions of our laboratories over a decade, it is diffi
cult to acknowledge in person the personnel involved in the studies at the
scientific, technical, illustrative and secretarial stages. We have been partic
ularly fortunate to have enjoyed working with many excellent technicians,
secretaries and illustrators and we hope that the preparation of this volume
does justice to their work.
No scientific study is possible without money and we wish to acknowl
edge the support of the National Health and Medical Research Council of
Australia, the Ford Foundation, the National Institutes of Health in the
United States and the Expanded Programme of Research in Reproduction
of the World Health Organisation. The support of our institutions, Monash
University, the Medical Research Centre, Prince Henry's Hospital and the
Howard Florey Institute of Physiology and Experimental Medicine was
vital in the work described.
It is also important to acknowledge the participation of numerous pa
tients in the studies described. Without their help, clinical research would
not be possible and quite often their misfortune prompted a new study or
helped to elucidate a novel concept.
Finally, and perhaps of greatest importance, we would like to acknowl
edge the part played by our wives, Jan, Jenny and Norma, who provided a
stable home environment, enabling us to concentrate our endeavours, often
too greatly, on our research, teaching and patient care. Without their sacri
fice and that of our families, our contributions to this field would have been
considerably smaller.
David de Kretser
Henry Burger
Bryan Hudson
Contents
Patterns of Secretion and Metabolism of the Gonadotrophic
Hormones (H.G. Burger and V.W.K. Lee) I
1.1 Assay Methods . I
1.1.1 Human FSH, LH and Prolactin. I
1.1.2 Animal Gonadotrophins . 2
1.2 Patterns ofLH and FSH Secretion in Normal Men 3
1.3 Metabolic Clearance and Gonadotrophin Secretion Rates in
Normal Men. 6
1.3.l MCR and Production Rate of LH 6
1.3.2 MCR and Production Rate of FSH 9
1.3.3 Initial Clearance of Gonadotrophin Subunits 11
1.3.4 Effect of Renal Disease on MCR 11
1.4 Summary 11
2 Control of FSH and LH Secretion
(D.M. de Kretser, H.G. Burger and W.J. Bremner) . 12
2.1 Sites of Production ofFSH and LH 12
2.2 Hypothalamic Influences on FSH and LH Secretion 13
2.3 Influence of Testicular Feedback 23
2.3.1 Feedback Control ofLH . 23
2.3.2 Feedback Control ofFSH 25
2.4 Assays for Inhibin 28
2.4.1 Modified Steelman-Pohley Bioassay 28
2.4.2 Bioassays Using Castrate Rams 29
2.4.3 Bioassays In Vivo Using Rodents 30
2.4.4 In Vitro Bioassays for Inhibin . 31
2.5 Assay Specificity 32
2.6 Sources of Inhibin 34
2.7 Evidence for Inhibin from Immunisation Studies 40
2.8 Characteristics and Mode of Action of Inhibin . 41
2.9 Physiological Implications ofInhibin 42
2.10 Summary 43
3 Pituitary Testicular Axis During Pubertal Development
(V.W.K. Lee and H.G. Burger) 44
3.1 Studies in Men 44
X Contents
3.1.1 Changes During Fetal Life . . . . . . . . 44
3.1.2 Changes in the Newborn . . . . . . . . . 45
3.1.3 Changes During Childhood and Adolescence 45
3.1.4 Pituitary Responses to LHRH 48
3.2 Studies in Rats 53
3.2.1 Changes in LH, FSH and Testosterone Concentrations with
Age. 53
3.2.2 Relationship Between Age and Hormonal Levels 56
3.2.3 Changes in Testicular Histology with Age 56
3.2.4 Significance of Hormonal Changes in the Developing Rat. 57
3.3 Studies in Rams 60
3.3.1 Changes in FSH, LH, Prolactin and Testosterone
Concentrations with Age. 61
3.3.2 LH, FSH and Testosterone Responses to LHRH with Age . 63
3.3.3 Changes in Testicular Histology with Age 65
3.3.4 Significance of Hormonal Changes 66
3.4 Overall Comments 69
4 Changes in the Pituitary-Testicular Axis with Age
(H.W.G. Baker and B. Hudson) 71
4.1 Introduction 71
4.2 Methods. 72
4.2.1 Testing the Pituitary-Testicular Axis 72
4.2.2 Selection of Subjects 73
4.2.3 Statistical Methods 73
4.3 Summary of Results . 74
4.3.1 Virility, Testicular Size and Histology 74
4.3.2 Gonadotrophin and Sex Hormone Levels 76
4.3.3 Metabolic Clearance and Production Rates of Sex Steroids 76
4.3.4 Dynamic Tests of Gonadotrophin and Testosterone Secretion 79
4.4 Significance of Senescent Testicular Degeneration 80
4.4.1 Mechanism of Hormone Changes with Age 80
4.4.2 Further Studies . 81
4.4.3 Aetiology of Testicular Damage. 81
4.5 Clinical Relevance 82
4.6 Summary 82
5 Spermatogenesis and the Sertoli Cell
(K.A. Rich and D.M. de Kretser) 84
5.1 Spermatogenesis . . . . . . . . . 84
5.1.1 The Spermatogenic Cycle . . . . . 85
5.1.2 Kinetics of the Spermatogenic Process 87
5.1.3 Duration of Spermatogenesis . . . . 88
5.1.4 Requirements for Quantitation of Spermatogenesis . 88
5.2 The Sertoli Cell. . . . . . . . . . . . . . . . 89
Contents XI
5.2.1 Morphological Characteristics 89
5.2.2 Nucleus. 90
5.2.3 Cytoplasm. 91
5.2.4 Inter-Sertoli Cell Junctions 93
5.2.5 Sertoli Cell Maturation 95
5.2.6 Secretory Products 96
5.2.6.1 Seminiferous Tubule Fluid 96
5.2.6.2 Androgen-Binding Protein 97
5.2.6.3 Inhibin 99
5.2.6.4 Plasminogen Activator. 99
5.2.6.5 Other Secretory Products 99
5.2.7 Steroidogenic Activity . 100
5.2.8 Hormonal Regulation of Sertoli Cell Function 101
5.2.9 Actions of FSH on the Sertoli Cell . 102
5.2.10 Effects of Androgen on the Sertoli Cell . 103
5.2.11 Biochemical Changes Associated with Sertoli Cell Maturation 104
6 Leydig Cell Function (Y. Hodgson and B. Hudson) . 107
6.1 Introduction 107
6.2 Morphology of the Leydig Cell 108
6.3 Steroid Biosynthesis and Secretion 115
6.4 Regulation of Leydig Cell Function 118
6.5 Hormonal Regulation ofLH Receptors 121
6.5.1 LHRH and Leydig Cell Function 125
6.6 Leydig Cells and Spermatogenesis. 126
6.7 Androgens in Blood . 127
6.8 Abnormalities of Leydig Cell Function 128
6.8.1 Congenital Disorders 128
6.8.2 Acquired Disorders 130
6.8.2.1 Cirrhosis of the Liver 131
6.8.2.2 Chronic Renal Failure. 131
6.8.2.3 Age. 131
6.8.3 Testicular Disorders . 132
7 The Effect of Testicular Damage on Sertoli and Leydig Cell
Function (D.M. de Kretser and J.B. Kerr) . 133
7.1 In trod uction 133
7.2 Spermatogenic Damage and the Control of FSH Secretion 133
7.3 Sertoli Cell Function and Testicular Damage . . . . 135
7.4 Luteinising Hormone, Testosterone and Spermatogenic
Damage. 142
7.5 Leydig Cell Structure and Spermatogenic Damage 147
7.6 Leydig Cell Function and Testicular Damage 150
References . 155
Subject Index 185
1 Patterns of Secretion and Metabolism
of the Gonadotrophic Hormones
H.G.Burger and V.W.K.Lee
The dominance of the female as an object of study in the science of re
productive biology is nowhere more clearly emphasised than in the intro
duction to a chapter on the secretion and metabolism of the gonadotrophic
hormones, as these relate to the pituitary-testicular axis: the commonly ac
cepted names of these hormones refer to their functions in female reproduction!
Luteinising hormone (LH) is also called by a little-used name relevant to
the male (interstitial cell-stimulating hormone, ICSH) but there is no counter
part for follicle-stimulating hormone (FSH) or prolactin (Prl). In this chapter,
the methods of gonadotrophin assay used in our laboratories are described
and the results are reviewed of their application to studies of their patterns
of secretion and metabolism.
1.1 Assay Methods
1.1.1 Human FSH, LH and Prolactin
The basic concepts regarding secretion of gonadotrophins were established
by application of bioassay procedures long before the advent of radioimmuno
assay. It has generally been held that gonadotrophin secretion commences
at puberty and there is evidence that gonadotrophin levels are lowered by
pituitary lesions and elevated in primary testicular disorders. The develop
ment of radioimmunoassays for pituitary hormones began with human growth
hormone (Greenwood 1962; Utiger et al. 1962; Roth et al. 1963) and was soon
followed by assays for LH (Midgley 1965, 1966; Bagshawe et al. 1966; Fran
chimont 1966a,b,c) and for FSH (Franchimont 1966a,b; Faiman and Ryan
1967). Results obtained with these assays quickly confirmed some of these
concepts, but have led to a greatly increased understanding of gonadotrophin
secretion and to the generation of new concepts not previously anticipated.
We developed our first gonadotrophin assay for LH, using paper chro
mato-electrophoresis as the separation method for bound and free hormone;
this development was dependent on the generous gift of highly purified LH
from Dr. Anne Stockell-Hartree, of the Department of Biochemistry, Cam
bridge University, U.K. (Burger et al. 1968). A method for LH using anti
body-coated tubes to immobilise the antibody and thus the bound hormone
was developed at about the same time (Catt et al. 1968).
More recently we have used double antibody radioimmunoassays, which
have been adopted routinely for human FSH, LH and prolactin (Alford et