Deciphering Growth (eBook)

Preface 5
Contents 7
Contributors 9
Evolutionary Trends in Body Size 14
Summary 14
Introduction 14
Body size trends 17
Identifying trends 18
Body size and diversity 24
Human impacts 27
Conclusions 28
Acknowledgements 29
References 29
Sexual Dimorphism in the Growth of Homo sapiens: Facts, Inferences and Speculation 32
Summary 32
Introduction 32
Sexual dimorphism in primates 33
Sexual dimorphism in H. sapiens 35
Molecular and biochemical basis for dimorphic growth 36
References 38
Genetic Control of Size at Birth 40
Summary 40
Introduction 41
Maternal uterine environment 42
Maternal genes and size at birth 43
Fetal genes and size at birth 45
Conclusions 47
References 49
The GH/ IGF- 1 Axis: Insights from Animal Models 54
Summary 54
Introduction 54
Insulin- like pathways control growth 56
Somatotrope control of IGF and growth 57
IGF- 1R mutations in mice 59
Overview 62
References 62
Downstream Mechanisms of Growth Hormone Action 66
Summary 66
Introduction 66
JAK2 is essential for initiating GHR signaling 68
MAPK- ERK1/2 pathway in GHR signaling 68
Role of PI3K-AKT pathway in GH action 69
Critical role of STAT5b in mediating GH action 69
Conclusions 72
References 74
Growth Hormone Receptor Signaling and Differential Actions in Target Tissues Compared to IGF- I 78
Summary 78
Introduction 79
Receptors and Signaling Pathways 79
JAK STAT Pathway 80
MAP Kinase Pathway 80
Other Pathways 81
Bone Development and the Somatomedin Hypothesis Revisited 82
Muscle Growth And Differentiation 86
References 87
IGF- I and Brain Growth: Multifarious Effects on Developing Neural Cells and Mechanisms of Action 90
Summary 90
Introduction 90
IGF- I Transgenic and Gene- Targeted Mice 91
Diverse functions of IGF- I on multiple neural cell types 92
Mechanisms and Signaling Pathways for IGF- I Actions on Neural Cells 96
The PI3- Kinase Pathway and IGF Actions in the Brain 99
Conclusions 102
References 102
IGF- I Deficiency: Lessons from Human Mutations 108
Summary 108
Introduction 108
IGF- I gene mutations 109
Other mutations in the GH- IGF- I axis causing IGF- I deficiency and GH insensitivity 112
Conclusions 115
References 116
Putting IGF- I Biology into a Clinical Perspective 120
Introduction 120
IGF Parameters for the Diagnosis of GH Deficiency 121
Monitoring IGF- I levels on GH treatment 122
Cross-sectional Survey of IGF Monitoring 126
Conclusions 127
References 131
IGF Resistance: The Role of the Type 1 IGF Receptor 134
Summary 134
Introduction 135
References 141
The Importance of the National Cooperative Growth Study ( NCGS) 144
Introduction 144
History 144
The NCGS Today 145
NCGS Substudies 146
NCGS Targeted Events 147
Importance of the NCGS: Conclusions 149
References 149
Appendix 1 150
Why we are Treating Children with Growth Hormone: Lessons from the French Registry 156
Summary 156
Introduction 156
Conclusion 162
Acknowledgments 162
References 162
Subject Index 166