Table Of ContentRESEARCH AND PERSPECTIVES IN ENDOCRINE INTERACTIONS
J.-C. Carel P.A. Kelly Y. Christen (Eds.)
Deciphering Growth
With 42 Figures and 14 Tables
123
Jean-Claude Carel, M.D. Yves Christen, Ph.D.
Hôpital Saint Vincent de Paul Fondation IPSEN
INSERM U.561 − Pour la Recherche Thérapeutique
Service d‘Endocrinologie Pédiatrique 24, rue Erlanger
Groupe Hospitalier Cochin-Saint Vincent 75781 Paris Cedex 16
de Paul-La-Roche Guyon France
74 à 82, Av Denfert Rochereau E-mail: [email protected]
75674 Paris Cedex 14
France
E-mail: [email protected]
Paul A. Kelly, Ph.D.
Inserm U584
Faculté de Médecine Necker
Enfants Malades
156, Rue de Vaugirard
75730 Paris Cedex 15
France
E-mail: [email protected]
ISSN 10 3-540-26192-3 Springer-Verlag Berlin Heidelberg New York
ISBN 13 978-3-540-26192-6 Springer-Verlag Berlin Heidelberg New York
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Preface
Growth is a complex process that is essential to life. Not only does size play an
important role in the process of cellular proliferation, but body size is also a
critical factor in determining which organisms live longer. Evolution has been
characterised by a dramatic increase in an organism’s body size, which is not
only limited to the size of the brain.
In mammals, the major factors involved in the regulation of body growth
are known: insulin-like growth factors (IGF) are key regulators of somatic
growth. Growth hormone (GH), secreted by the pituitary gland, directly re-
gulates circulating levels of IGF-I, which is the major coordinator of spatio-
temporal growth of the organism. In humans, growth is even more complex,
involving a number of specific characteristics not found in other species.
These include rapid intrauterine growth, deceleration just after birth, a mid-
childhood growth spurt, a second deceleration before puberty, an adolescent
growth spurt, and finally full statural growth, which is seen somewhat later.
The combined knowledge concerning the endocrine and paracrine aspects of
growth have led to the introduction of treatment regimens, most effective in
GH-deficient children. However, size depends on the combination of a num-
ber of genetic factors, and there remain several aspects of this complex pro-
cess still poorly understood.
The Fondation Ipsen organized the fourth meeting in a series on Research
and Perspectives in Endocrine Interactions entitled Deciphering Growth (Par-
is, December 6, 2004). The one-day meeting held in Paris was divided into
three general sessions. The first, Evolution and genetics of growth, included
talks on evolutionary trends in body size, the human evolution of gender-
specific growth patterns, and the genetic control of body size at birth. The
second general session was on the GH – IGF-I axis. Six speakers covered this
broad subject, with presentations on isoforms of the GH receptor and growth
in normal and pathological conditions, the use of mouse models to under-
stand the role of the IGF-I receptor in growth, GH receptor downstream sig-
nalling, differential actions of GH and IGF-I in target tissues, the regulation of
brain growth by IGF-I via direct effects on neural progenitor cell proliferation
and survival, and phenotypes associated with human IGF-I gene deletion.
The final session was on Clinical approaches. The first two speakers covered
the clinical perspective of measurement of circulating IGF-I levels and the
importance of mutations of the type 1 IGF receptor in IGF-I resistance. The
last two talks described the importance of national growth registries to pedia-
VI Preface
tric research, the French registry and the National Cooperative Growth Study
(NCGS).
P. Kelly
J.C. Carel
Y. Christen
P.S. The editors wish to thank Mrs. Jacqueline Mervaillie for the organization of
the meeting and Mrs. Mary Lynn Gage and Mrs. Astrid de Gérard for the editing
of the book.
Contents
Evolutionary Trends in Body Size
Andy Purvis and C. David L. Orme . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Sexual Dimorphism in the Growth of Homo sapiens:
Facts, Inferences and Speculation
Ron G. Rosenfeld . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Genetic Control of Size at Birth
David B. Dunger, C.J. Perty, and K.K. Ong . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
The GH/IGF-1 Axis: Insights from Animal Models
Martin Holzenberger, Laurent Kappeler,
Carlos De Magalhaes Filho, and Yves Le Bouc . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Downstream Mechanisms of Growth Hormone Actions
Vivien Hwa and Ron G. Rosenfeld . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Growth Hormone Receptor Signaling and Differential Actions
in Target Tissue Compared to IGF-I
Paul A. Kelly, Anne Bachelot,
Athanassia Sotiropoulos, and Nadine Binart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
IGF-I and Brain Growth:
Multifarious Effects on Developing Neural Cells
and Mechanisms of Actions
Teresa L. Wood, Terra J. Frederick, and Jennifer K. Ness . . . . . . . . . . . . . . . . . . . 77
IGF-I Deficiency: Lessons from Human Mutations
Martin O. Savage, Cecilia Camacho-Hübner, Marie-José Walenkamp,
L.A. Metherell, A. David, L.A. Pereira, Adam Denley,
A.J.L. Clark, and Jan Maarten Wit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Putting IGF-I Biology into a Clinical Perspective
Peter E. Clayton, U. Das, and A.J. Whatmore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
VIII Contents
IGF Resistance: The Role of the Type 1 IGF Receptor
Steven D. Chernausek, M. Jennifer Abuzzahab, Wieland Kiess,
Doreen Osgood, Anke Schneider, and Robert J. Smith . . . . . . . . . . . . . . . . . . . . . . 121
The Importance of the National Cooperative Growth Study (NCGS)
Raymond L. Hintz . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Why are we Treating Children with Growth Hormone
Jean Claude Carel and Jean-Louis Chaussain . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Contributors
Abuzzahab, Jennifer
Children‘s Hospitals and Clinics,
St. Paul, Minnesota,
USA
Bachelot, Anne
Inserm U584, Faculté de Médecine Necker,
156, Rue de Vaugirard, 75730 Paris Cedex 15,
France
Binart, Nadine
Inserm U584, Faculté de Médecine Necker,
156, Rue de Vaudirard, 75730 Paris Cedex 15,
France
Camacho-Hübner, Cecilia
Research Centre in Clinical and Molecular Endocrinology,
William Harvey Research Institute,
Queen Mary’s School of Medicine and Dentistry,
Queen Mary’s University of London, London,
UK
Carel, Jean-Claude
Pediatric Endocrinology and Inserm U561,
Groupe hospitalier Cochin-Saint Vincent de Paul,
82 av Denfert Rochereau, 75014 Paris,
France
Chaussain, Jean-Louis
Pediatric Endocrinology and Inserm U561,
Groupe hospitalier Cochin-Saint Vincent de Paul,
82 av Denfert Rochereau, 75014 Paris,
France
X Contributors
Chernausek, Steven D.
University of Cincinnati School of Medicine,
Cincinnati Children‘s Hospital Medical Center,
Division of Endocrinology,
3333 Burnet Ave., Cincinnati OH 45229,
USA
Clark, A.J.L.
Department of Endocrinology, Barts and the London,
Queen Mary’s University of London, BEM Unit, London,
UK
Clayton, Peter E.
Academic of Child Health, Division of Human Development
and Reproductive Health, The Medical School, University of Manchester,
Manchester M13 9PT,
UK
Das, U.
Academic of Child Health, Division of Human Development
and Reproductive Health, The Medical School, University of Manchester,
Manchester M13 9PT,
UK
David, A.
Department of Paediatric Endocrinology, St Bartholomew‘s Hospital,
West Smithfield, London EC1A 7BE,
UK
De Magalhaes Filho, Carlos
Inserm U515, Hôpital Saint-Antoine, 75571 Paris 12,
France
Denley, Adam
School of Molecular and Biomedical Science, University of Adelaide,
Adelaide,
Australia
Dunger, David B.
Department of Paediatrics, University of Cambridge,
Addenbrooke‘s Hospital, Box 116 Level 8,
Hills Road, Cambridge CB2 2QQ,
UK
