The Growth Hormone/Insulin-Like Growth Factor Axis During Development

420 Pages·2005·41.46 MB·English

by  Julie A. Chowen (auth.), Isabel Varela-Nieto PhD

THE GROWTH
HORMONE/INSULIN-LIKE
GROWTH FACTOR AXIS DURING
DEVELOPMENT
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
IRUN R. COHEN, The Weizmann Institute of Science
DAVID KRITCHEVSKY, Wistar Institute
ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research
RODOLFO PAOLETTI, University of Milan
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THE GROWTH HORMONE/INSULIN-LIKE GROWTH FACTOR AXIS
DURING DEVELOPMENT
Edited by Isabel Varela-Nieto and Julie A. Chowen
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THE GROWTH
HORMONE/INSULIN-LIKE
GROWTH FACTOR AXIS DURING
DEVELOPMENT
edited by
ISABEL VARELA-NIETO, PhD
Instituto de Investigaciones Biomedicas ''Alberto Sols''
Consejo Superior de Investigaciones Cientificas (IIB-CSIC)
Universidad Autonoma de Madrid (UAM)
Arturo Duperier 4. 28029 Madrid, Spain
JULIE A. CHOWEN, PhD
Hospital Infantil Universitario Nino Jesus
Department of Endocrinology and Investigation
Menendez Pelayo, 65, 28009 Madrid, Spain
Springer
Isabel Varela-Nieto, PhD Julie A. Chowen, PhD
Instituto de Investigaciones Biomedicas "Alberto Sols" Hospital Infantil Universitario Nifio Jesus
Consejo Superior de Investigaciones Cientificas Department of Endocrinology and Investigation
(IIB-CSIC) Menendez Pelayo, 65, 28009 Madrid, Spain
Universidad Autonoma de Madrid (UAM)
CONTENTS
INTRODUCTION vi
1. BASIC PHYSIOLOGY OF THE GROWTH HORMONE/
INSULIN-LIKE GROWTH FACTOR (IGF).AXIS 1
Laura M. Frago and Julie A. Chowen
2. EXPERIMENTAL MODELS FOR UNDERSTANDING THE ROLE
OF INSULIN-LIKE GROWTH FACTOR-I AND ITS RECEPTOR
DURING DEVELOPMENT 27
Jose Luis Trejo, Eva Carro and Deborah J. Burks
3. INSULIN-LIKE GROWTH FACTOR BINDING PROTEINS
IN DEVELOPMENT 5
Josef V. Silha and Liam J. Murphy
4. GROWTH HORMONE, INSULIN-LIKE GROWTH FACTORS
AND THE FEMALE REPRODUCTIVE SYSTEM 91
Carolyn A. Bondy and Jian Zhou
5. SKELETAL MUSCLE 17
Ana M. Fernandez and Derek LeRoith
6. CARDIOVASCULAR AND RESPIRATORY SYSTEMS 149
Asa Tivesten and Jorgen Isgaard
7. HEMATOPOIESIS 167
Wilson Savino, Salete Smaniotto and Mireille Dardenne
8. BRAIN DEVELOPMENT 187
Gregory J. Popken, Martha Dechert-Zeger, Ping Ye, A. Joseph D'Ercole
9. REGULATION OF VERTEBRATE SENSORY ORGAN DEVELOPMENT:
A SCENARIO FOR GROWTH HORMONE AND INSULIN-LIKE
GROWTH FACTORS ACTION 21
Amelia Diaz-Casares, Yolanda Leon, Enrique J. de la Rosa & Isabel Varela-Nieto
10. ROLE OF INSULIN-LIKE GROWTH FACTORS IN NEURONAL
PLASTICITY AND NEUROPROTECTION 243
Ignacio Torres Aleman
IL AGING AND LIFE SPAN 259
Holly M. Brown-Borg
12. INTERACTIONS OF INSULIN-LIKE GROWTH FACTOR-I AND
ESTROGEN IN THE BRAIN 285
Pablo Mendez, Gloria Patricia Cardona-Gomez and Luis Miguel
Garcia-Segura
13. CANCER 305
Adda Grimberg
14. GENETIC BASIS OF PROPORTIONAL SHORT STATURE 341
Angel Campos-Barros, Karen E. Heath, Jesus Argente
15. FUTURE PERSPECTIVES: FROM STEM CELLS AND IGF
BIOLOGY TO THE CLINIC 385
Yvan Arsenijevic
INDEX 413
INTRODUCTION
Although growth hormone (GH) was discovered in 1921, it was
not until the 1950s that investigators began to suspect that some of its
effects on growth were not direct but involved a mediating factor.
Indeed, after the discovery of insulin-like growth factor (IGF) it was
thought that most, if not all, GH effects involved stimulation of IGF-I
production. However, it is now accepted that GH and IGF have both
common and individual roles in growth, development and metabolism.
The IGF family, comprised of insulin and two factors similar to
insulin termed IGF-I and IGF-II, has pleiotropic functions in mammals.
The first member of this family to be identified was insulin, with
subsequent investigation resulting in the elucidation of its role in glucose
metabolism and its implication in the etiology of diabetes mellitus. This
discovery effected an explosion in the investigation of the structure,
function, and mechanisms of action of insulin. The enormous interest in
this molecule resulted in the concession of three Nobel Prizes for the
investigation of insulin: in 1923 for the discovery of its capacity to treat
diabetes, in 1958 for the first sequence of a protein and in 1963 for the
first determination of the three-dimensional structure of a protein. Hence,
the investigation of insulin has been a pioneer in many scientific fields.
Likewise, the insulin receptor was the first receptor with tyrosine kinase
activity to be identified and cloned, and is the prototype of membrane
receptors with enzymatic activity. Consequently, the mechanisms of
action of this receptor have been the focus of intense study leading to the
identification of intracellular signaling pathways in response to members
of this protein family and has lead, once again, to the discovery of new
molecules, pathways and signaling cascades that has had important
reverberations in other scientific fields.
Later, the IGFs were discovered and found to be intricately
involved in embryonic development and postnatal growth. This was
followed by the discovery of a family of binding proteins (IGFBPs) that
not only transport the IGFs in the circulation, but alter their function and
biological activity. Such widespread and intricate regulation further
emphasized the importance of these growth factors in normal
physiology. The enormous interest in the insulin-IGF family of proteins
lead to the generation of the first double and triple knock-out animals.
These knock-out animals, null for a combination of the IGFs, their
receptors and the BPs, has helped to shed light on the differential roles of
these molecules and their importance in growth and embryonic
development. These studies also demonstrated new and diverse functions
for these factors, amongst which their activities in the nervous system is
noteworthy. Advances in the understanding of the expression, function,
and structure of these factors has not only helped us to further our
knowledge of embryonic and postnatal growth, but has also opened the
door to new possibilities for their therapeutic use in the treatment of
growth alterations, in neurodegeneration, and regenerative medicine.
The objective of this volume is to explain our current
understanding regarding the cellular actions of these factors and how this
basic knowledge has contributed to our comprehension of their
implications in distinct illnesses, as well as the possibility for the
development of new therapies.
Chapter 1 covers the basic physiology of the GH/IGF axis, while
Chapter 2 discusses some of the most widely used experimental models
that have helped to determine the roles of the various members of this
axis. The role of IGFBPs in brain and other tissues is discussed in
Chapter 3. The importance of IGFs in brain development and function is
dealt with in various chapters, all with an individual focus. Chapter 8
covers overall brain development and the effect that each component of
the GH/IGF-I system exerts in this process. The trophic effects that IGFs
have on neurons in the mature brain and the protection that they exert
during neurodegenerative processes or assaults by noxious substances is
addressed in Chapter 10 and the interaction of IGFs with other trophic
factors in Chapter 12. Chapter 9 focuses specifically on IGFs in
neurosensory systems. The effect of the GH/IGF axis in the reproductive
tract, skeletal muscle, cardiovascular system and hematopoeisis are
addressed in Chapters 4-7. Two areas of current interest include the
influence of IGF-I on aging and its possible role in cancer. These
subjects are affronted in Chapters 11 and 13, respectively. In Chapter 14
the growing information regarding genetic implications in human
growth, involving almost all members of the GH/IGF axis, is presented.
The final chapter deals with a new and exciting area of investigation: the
use of stem cells in investigation and the possible treatment of a variety
of illnesses. This is a rapidly advancing field and future developments
will necessitate the need for a second edition.
We would like to express our sincere gratitude to all of the
authors for taking time out of their busy schedules to participate in this
project. In addition, we would like to acknowledge and thank our
colleagues that have generously donated their time and experience to act
as reviewers in order to improve the scope and focus of this book. We
are in debt to all.
Isabel Varela-Nieto and Julie A. Chowen
Chapter 1
BASIC PHYSIOLOGY OF THE GROWTH
HORMONE/INSULIN-LIKE GROWTH FACTOR
AXIS
Laura M, Frago and Julie A. Chowen
Hospital Infantil Universitario Nino Jesus, Universidad Autonoma de Madrid, Departamento
de Endocrinologia, Menendez Pelayo, 65, 28009 Madrid, Spain
Key words: Binding proteins; growth hormone-releasing hormone; intracellular signaling;
receptor; somatostatin.
1. INTRODUCTION
The growth hormone (GH)/insulin-like growth factor (IGF) axis is
intimately involved in the integration of a multitude of signals that regulate
systemic growth and metabolism throughout fetal and postnatal
development. In the adult animal, maintenance of metabolic balance and
cellular integrity, as well as involvement in normal tissue regeneration and in
response to injury, can also be attributed to GH and the IGFs.
The classical components of this axis, including GH, the GH receptor
(GHR), the GH binding proteins (GHBPs), IGF-I, IGF-II, IGF receptors and
the six IGF binding proteins (IGFBPs), will be described briefly in this
chapter. Although GH is produced mainly by the anterior pituitary, its
receptor is expressed in many tissues throughout the organism^"^, indicating
that this hormone can have widespread effects. In contrast, the IGFs are
produced by most tissues during both fetal and postnatal life, with both the
circulating and locally produced factors having physiological functions"^'^.