The Leydig cell in health and disease

485 Pages·2007·12.947 MB·English

by  Anita H Payne, Matthew Phillip Hardy

CONTEMPORARY ENDOCRINOLOGY™
Payne
P. Michael Conn, Series Editor
CONTEMPORARY ENDOCRINOLOGY™
Hardy
The Leydig Cell in Health and Disease
T TThhee
Edited by
Ah
Anita H. Payne,
PhD
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Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA
d
Matthew P. Hardy,
PhD L
Population Council, Center for Biomedical Research, New York, NY r LLeeyyddiigg CCeellll
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y
Nearly 10 years after they published the first book devoted entirely to the Leydig cell, Anita Payne and g
Matthew Hardy have collaborated again to provide a comprehensive study of this fascinating and important d
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cell type. The Leydig Cell in Health and Disease presents all of the developments in our understanding of
ni
Leydig cell biology and explores a wide variety of current and potential clinical applications. All aspects of g
Leydig cell biology, development, regulation, and physiology are explored in expertly written chapters. The iinn HHeeaalltthh
E
Leydig Cell in Health and Disease explores topics of great interest to the private sector, including the C
possible application of steroidogenesis discoveries to androgen synthesis or suppressing Leydig cell function x
e
as a key mechnanism in the development of a male contraceptive. This in-depth volume is an invaluable c
resource for information on the science and application of Leydig cell biology and function. l
e
l
s aanndd DDiisseeaassee
Features i
sn
(cid:1) Explores current and future clinical applications (cid:1) Presents Leydig cell developments
of Leydig cell function in key cellular processes from a rigorous scientific application, with DH
additional emphasis on clinical applications
(cid:1) Examines toxins and other environmental ie
s
factors that interfere with Leydig cell function
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o
Contents rl
t
d
Part I. Historical.A History of Leydig Cell Research. Factors in Leydig Cell Function. Insulin-Like Peptide 3 h
e
Part II. Cell Biology. Structural and Histological in Leydig Cells. Neuronal Signaling Molecules and

Analysis of Leydig Cell Steroidogenic Function. Fetal Leydig Cells. Regulation of Leydig Cell Function as it ra
Leydig Cells: Origin, Regulation, and Functions.Regu- Pertains to the Inflammatory Response. Activins and s
n
lation of Leydig Cells During Pubertal Development. Leydig Cell Development, Differentiation, and Disease. Edited by
The Human Leydig Cell: Functional Morphology and Transcription Factors as Regulators of Gene Expres- id
Developmental History.Dynamics of Leydig Cell Regen- sion During Leydig Cell Differentiation and Function. n
eration After EDS: A Model for Postnatal Leydig Cell Androgen Receptor in Leydig Cell Function and Devel-

Development. Aging and the Decline of Androgen opment. Part V. Physiology and Applied Aspects. WD Anita H. Payne, PhD
Production. Part III Steroidogenesis. Regulation of Fluid Exchange and Transport of Hydrophilic Factors in
i
Leydig Cell Cholesterol Metabolism. The Role of StAR the Testis. Immortalized Leydig Cell Lines as Models s
o
in Leydig Cell Steroidogenesis. Steroidogenic Enzymes for Studying Leydig Cell Physiology. Induction of Leydig Matthew P. Hardy,
in Leydig Cells. Development of Leydig Cell Steroido- Cell Tumors by Xenobiotics. Environmental Factors me PhD
genesis. Peripheral Testosterone Metabolism. Leydig That Disrupt Leydig Cell Steroidogenesis. The Leydig a
Cell Aromatase: From Gene to Physiology.The Role of Cell as a Target for Male Contraception. Clinical Evalu-
e
s
Estrogen Sulfotransferase in Leydig Cells. Endocrinol- ation of Leydig Cell Function. Index.
n
ogy of Leydig Cells in Nonmammalian Vertebrates. e
Part IV. Regulation.The Luteinizing Hormone Recep-
tor. Insights Into Leydig Cell Function From Mice With
Genetically Modified Gonadotropin Action. Growth
Contemporary Endocrinology™
THE LEYDIG CELL IN HEALTH AND DISEASE
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E-ISBN: 978-1-59745-453-7
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HE EYDIG
C H
ELL IN EALTH
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AND ISEASE
Edited by
A H. P ,
NITA AYNE PhD
Department of Obstetrics and Gynecology
Stanford University School of Medicine
Stanford, CA
M P. H ,
ATTHEW ARDY PhD
Population Council
Center for Biomedical Research
New York, NY
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The Leydig cell in health and disease / edited by Anita H. Payne, Matthew P. Hardy.
p. ; cm. — (Contemporary endocrinology)
Includes bibliographical references and index.
ISBN: 978-1-58829-754-9 (alk. paper)
1. Leydig cells. I. Payne, Anita H. (Anita Hart) II. Hardy, Matthew Phillip. III. Series: Contemporary endocrinology (Totowa, N.J. : Unnumbered)
[DNLM: 1. Leydig Cells—physiology. 2. Testis—physiology. WJ 830 L681 2007]
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2006026866
P
REFACE
Ten years ago, in association with Lonnie Russell, we We know more about the process of cholesterol trans-
published The Leydig Cell (Cache River Press, Vienna port to the inner mitochondrial membrane and site of
IL). It was the first volume of its kind, devoted entirely side-chain cleavage, the rate-limiting step in testoster-
to review chapters covering basic and clinical aspects of one biosynthesis. It appears in 2006 to be like a Virginia
Leydig cell structure and function. As editors, it became reel dance in which the precursor, cholesterol, may ar-
clear to us that such a book filled a gap in the literature rive with one binding partner, the steroid acute regula-
on male reproduction. The testis produces both sperm tory protein, but finish with another, the peripheral
and testosterone, and the two are linked because sper- benzodiazepine receptor, which has been clearly shown
matogenesis is critically dependent on androgen action. to form a pore in the mitochondrial membrane. How the
However, the role of the Leydig cell in synthesizing the cytosol to mitochondrial membrane transfer occurs
male hormone can be lost in the beautiful and complex remains an actively debated research topic.
series of cellular events leading to the formation of We are also on the verge of a new male contraceptive
sperm. In addition, Leydig cells, which are far outnum- after more than 30 years of studying the hormonal
bered by the germ cell population, constitute only 5 to approach. Essentially, this method will involve using
15% of the testicular volume (depending on the species). androgen in combination with another sex steroid to
Despite their minority status in the testis, knowledge of impose negative feedback on the hypothalamus and
the biology of Leydig cells is an essential prerequisite to pituitary Leydig cell function will then be suppressed,
understanding male fertility, sexual function, and repro- lowering testicular testosterone levels below the thresh-
ductive health. And yet, there was no centralized reposi- old needed to sustain spermatogenesis. It will soon be
tory for that knowledge. The first book, then, was an known whether this is an effective product and one that
attempt to fill this unmet need. will find a niche in the marketplace. Meanwhile, use and
Ten years have passed and science has advanced, but abuse of androgen for its effects as an anabolic steroid to
the question arises as to why it would be appropriate and increase muscle mass is a phenomenon among profes-
advisable to publish a second volume, again focusing on sional athletes and teenage boys. The fertility-suppressing
this one cell type. We would argue that successes in the effects of exogenous androgen are a potential, if unrecog-
field have created a new gap. In each of the 30 chapters nized, concern within this group.
of The Leydig Cell in Health and Disease, we aim to Whereas boys and younger men seek to boost andro-
provide closure while simultaneously pointing to new gen levels above normal, a potentially more legitimate
possibilities. We hope to make the case that the Leydig trend exists for men that are aging. With aging, androgen
cell merits the reader’s time and attention as much as it levels decrease as a result of atrophic changes in Leydig
did in 1996. It would be difficult to highlight some of the cells. Administering testosterone can counteract the de-
developments that made the new book worthwhile with- cline. Longitudinal studies, currently in progress,
out going beyond the scope of a preface and writing a involving testosterone replacement in the aging male will
31st chapter. In more recent years the crystal structures become more acceptable if proven beneficial and safe.
of a gonadotropin receptor and several of the steroid It is now more apparent than it was in 1996 that expo-
synthesizing and metabolizing enzymes have been sure to environmental toxicants interferes with Leydig
solved. In some cases, research groups working at cell function. Some of the toxicants in this category,
biopharmaceutical companies achieved the structure termed endocrine disruptors, are now known to antago-
solutions. Obviously, the potential for applying results nize testosterone synthesis (phthalate esters, for ex-
related to androgen synthesis to drug development and ample). It is of vital importance to put all of the above
therapy has not gone unnoticed in the private sector. developments into a rigorous scientific perspective, and
v
vii Preface
the present volume has additional emphasis on clinical production. We also are grateful to Michael Conn for
applications. We hope to have succeeded in this en- leading us to Humana Press and for including The Leydig
deavor. Special thanks are due to Meghan Howard and Cell in Health and Disease in the Contemporary Endo-
Jean Schweis at the Population Council for their exper- crinology™ series. Finally, we thank the authors and
tise in the management of the manuscripts as they were commend their work to our readers.
received from the authors, and to Richard Lansing of Anita H. Payne
Humana Press for his expert advice during all phases of Matthew P. Hardy
C
ONTENTS
Preface........................................................................................................................................... v
Contributors................................................................................................................................ix
List of Color Plates.....................................................................................................................xi
PART I. HISTORICAL
1. A History of Leydig Cell Research............................................................................................. 3
A. Kent Christensen
PART II. CELL BIOLOGY
2. Structural and Histological Analysis of Leydig Cell Steroidogenic Function......................... 33
Syed G. Haider, Gisela Servos, and Nicole Tran
3. Fetal Leydig Cells: Origin, Regulation, and Functions............................................................ 47
Humphrey Hung-Chang Yao and Ivraym Barsoum
4. Regulation of Leydig Cells During Pubertal Development...................................................... 55
Renshan Ge and Matthew P. Hardy
5. The Human Leydig Cell: Functional Morphology and Developmental History..................... 71
Frederick P. Prince
6. Dynamics of Leydig Cell Regeneration After EDS: A Model for Postnatal Leydig Cell
Development .......................................................................................................................... 91
Katja Teerds and Eddy Rijntjes
7. Aging and the Decline of Androgen Production..................................................................... 117
Haolin Chen, Andrew Midzak, Lin-di Luo, and Barry R. Zirkin
PART III. STEROIDOGENESIS
8. Regulation of Leydig Cell Cholesterol Metabolism............................................................... 135
Salman Azhar and Eve Reaven
9. The Role of StAR in Leydig Cell Steroidogenesis................................................................. 149
Douglas M. Stocco
10. Steroidogenic Enzymes in Leydig Cells ................................................................................. 157
Anita H. Payne
11. Development of Leydig Cell Steroidogenesis......................................................................... 173
Peter J. O’Shaughnessy, Heather Johnston, and Paul Joseph Baker
12. Peripheral Testosterone Metabolism....................................................................................... 181
Daniel P. Sherbet and Richard J. Auchus
13. Leydig Cell Aromatase: From Gene to Physiology................................................................ 189
Serge Carreau
14. The Role of Estrogen Sulfotransferase in Leydig Cells ......................................................... 197
Wen-Chao Song
15. Endocrinology of Leydig Cells in Nonmammalian Vertebrates ............................................ 207
Kelly Bonner Engel and Gloria Vincz Callard
vii
viii Contents
PART IV. REGULATION
16. The Luteinizing Hormone Receptor........................................................................................ 227
Maria L. Dufau and Chon-Hwa Tsai-Morris
17. Insights Into Leydig Cell Function From Mice With Genetically Modified
Gonadotropin Action........................................................................................................... 253
Ilpo Huhtaniemi
18. Growth Factors in Leydig Cell Function................................................................................. 263
Varadaraj Chandrashekar and Andrzej Bartke
19. Insulin-Like Peptide 3 in Leydig Cells .................................................................................. 279
Richard Ivell and Ross A. D. Bathgate
20. Neuronal Signaling Molecules and Leydig Cells ................................................................... 291
Artur Mayerhofer
21. Regulation of Leydig Cell Function as it Pertains
to the Inflammatory Response ............................................................................................ 305
Dale B. Hales
22. Activins and Leydig Cell Development, Differentiation, and Disease.................................. 323
Gail P. Risbridger and Christopher Butler
23. Transcription Factors as Regulators of Gene Expression During Leydig Cell
Differentiation and Function............................................................................................... 333
Jacques J. Tremblay
24. Androgen Receptor in Leydig Cell Function and Development............................................ 345
Stephen M. Eacker and Robert E. Braun
PART V. PHYSIOLOGY AND APPLIED ASPECTS
25. Fluid Exchange and Transport of Hydrophilic Factors in the Testis........................................... 365
Brian Peter Setchell
26. Immortalized Leydig Cell Lines as Models for Studying Leydig Cell Physiology............... 373
Mario Ascoli
27. Induction of Leydig Cell Tumors by Xenobiotics.................................................................. 383
Paul M. D. Foster
28. Environmental Factors That Disrupt Leydig Cell Steroidogenesis........................................ 393
Vassilios Papadopoulos
29. The Leydig Cell as a Target for Male Contraception............................................................ 415
Craig Marc Luetjens, Joachim Wistuba, Gerhard Weinbauer,
and Eberhard Nieschlag
30. Clinical Evaluation of Leydig Cell Function.......................................................................... 443
Ronald S. Swerdloff and Christina Wang
Index......................................................................................................................................... 459
C
ONTRIBUTORS
MARIO ASCOLI, PhD • Department of Pharmacology, Carver College of Medicine, The University of Iowa,
Iowa City, IA
RICHARD J. AUCHUS, MD, PhD • Division of Endocrinology and Metabolism, Department of Internal Medicine,
University of Texas Southwestern Medical Center, Dallas, TX
SALMAN AZHAR, PhD • Geriatric Research, Educationnn and Clinical Center (GRECC), VA Palo Alto Health Care
System,, Palo Alto, CA; and Division of Gastroenterology and Hepatology, Department of Medicine, Stanford
University School of Medicine, Stanford, CA
PAUL JOSEPH BAKER, PhD • Institute of Comparative Medicine, University of Glasgow Veterinary School,
Glasgow, UK
IVRAYM BARSOUM, MD, MS • Department of Veterinary Biosciences, University of Illinois, Urbana, IL
ANDRZEJ BARTKE, PhD • Department of Physiology, Southern Illinois University School of Medicine, Carbondale,
IL; and Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL
ROSS A. D. BATHGATE, PhD • Howard Florey Institute, University of Melbourne, Melbourne, Victoria, Australia
ROBERT E. BRAUN, PhD • Department of Genome Sciences, School of Medicine, University of Washington,
Seattle, WA
CHRISTOPHER BUTLER, PhD • Centre for Urological Research, Monash Institute of Medical Research, Monash
University, Melbourne, Clayton, Victoria, Australia
GLORIA VINCZ CALLARD, PhD • Department of Biology, Boston University, Boston, MA
SERGE CARREAU, PhD • Laboratoire Biochimie, USC2006 INRA-EA2608, IBFA-Université, Caen, France
HAOLIN CHEN, PhD • Division of Reproductive Biology, Department of Biochemistry and Molecular Biology,
Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
A. KENT CHRISTENSEN, PhD • Department of Cell and Developmental Biology, University of Michigan Medical
School, Ann Arbor, MI
VARADARAJ CHANDRASHEKAR, PhD • Department of Physiology, Southern Illinois University School of Medicine,
Carbondale, IL
MARIA L. DUFAU, MD, PhD • Section of Molecular Endocrinology, Endocrinology and Reproduction, Research
Branch, National Institutes of Child Health and Human Development, National Institutes of Health,
Bethesda, MD
STEPHEN M. EACKER, PhD • Department of Genome Sciences, School of Medicine, University of Washington,
Seattle, WA
KELLY BONNER ENGEL, PhD • Department of Biology, Boston University, Boston, MA
PAUL M. D. FOSTER, PhD • National Institute of Environmental Health Sciences, National Institutes of Health
Research, Triangle Park, NC
RESHAN GE, MD, MS • Center for Biomedical Research, Population Council and The Rockefeller University,
New York, NY
DALE B. HALES, PhD • Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL
MATTHEW P. HARDY, PhD • Center for Biomedical Research, Population Council
and The Rockefeller University, New York, NY
SYED G. HAIDER, PhD • Institute of Anatomy II, Heinrich Heine University, Duesseldorf, Germany
ILPO HUHTANIEMI, MD, PhD • Institute of Reproductive and Developmental Biology, Imperial College London,
London, UK
RICHARD IVELL, PhD • School of Molecular and Biomedical Science, University of Adelaide, South Australia,
Australia
ix