1;Preface;5 2;Contents;7 3;Contributors;9 4;Evolutionary Trends in Body Size;14 4.1;Summary;14 4.2;Introduction;14 4.3;Body size trends;17 4.4;Identifying trends;18 4.5;Body size and diversity;24 4.6;Human impacts;27 4.7;Conclusions;28 4.8;Acknowledgements;29 4.9;References;29 5;Sexual Dimorphism in the Growth of Homo sapiens: Facts, Inferences and Speculation;32 5.1;Summary;32 5.2;Introduction;32 5.3;Sexual dimorphism in primates;33 5.4;Sexual dimorphism in H. sapiens;35 5.5;Molecular and biochemical basis for dimorphic growth;36 5.6;References;38 6;Genetic Control of Size at Birth;40 6.1;Summary;40 6.2;Introduction;41 6.3;Maternal uterine environment;42 6.4;Maternal genes and size at birth;43 6.5;Fetal genes and size at birth;45 6.6;Conclusions;47 6.7;References;49 7;The GH/ IGF- 1 Axis: Insights from Animal Models;54 7.1;Summary;54 7.2;Introduction;54 7.3;Insulin- like pathways control growth;56 7.4;Somatotrope control of IGF and growth;57 7.5;IGF- 1R mutations in mice;59 7.6;Overview;62 7.7;References;62 8;Downstream Mechanisms of Growth Hormone Action;66 8.1;Summary;66 8.2;Introduction;66 8.3;JAK2 is essential for initiating GHR signaling;68 8.4;MAPK- ERK1/2 pathway in GHR signaling;68 8.5;Role of PI3K-AKT pathway in GH action;69 8.6;Critical role of STAT5b in mediating GH action;69 8.7;Conclusions;72 8.8;References;74 9;Growth Hormone Receptor Signaling and Differential Actions in Target Tissues Compared to IGF- I;78 9.1;Summary;78 9.2;Introduction;79 9.3;Receptors and Signaling Pathways;79 9.4;JAK STAT Pathway;80 9.5;MAP Kinase Pathway;80 9.6;Other Pathways;81 9.7;Bone Development and the Somatomedin Hypothesis Revisited;82 9.8;Muscle Growth And Differentiation;86 9.9;References;87 10;IGF- I and Brain Growth: Multifarious Effects on Developing Neural Cells and Mechanisms of Action;90 10.1;Summary;90 10.2;Introduction;90 10.3;IGF- I Transgenic and Gene- Targeted Mice;91 10.4;Diverse functions of IGF- I on multiple neural cell types;92 10.5;Mechanisms and Signaling Pathways for IGF- I Actions on Neural Cells;96 10.6;The PI3- Kinase Pathway and IGF Actions in the Brain;99 10.7;Conclusions;102 10.8;References;102 11;IGF- I Deficiency: Lessons from Human Mutations;108 11.1;Summary;108 11.2;Introduction;108 11.3;IGF- I gene mutations;109 11.4;Other mutations in the GH- IGF- I axis causing IGF- I deficiency and GH insensitivity;112 11.5;Conclusions;115 11.6;References;116 12;Putting IGF- I Biology into a Clinical Perspective;120 12.1;Introduction;120 12.2;IGF Parameters for the Diagnosis of GH Deficiency;121 12.3;Monitoring IGF- I levels on GH treatment;122 12.4;Cross-sectional Survey of IGF Monitoring;126 12.5;Conclusions;127 12.6;References;131 13;IGF Resistance: The Role of the Type 1 IGF Receptor;134 13.1;Summary;134 13.2;Introduction;135 13.3;References;141 14;The Importance of the National Cooperative Growth Study ( NCGS);144 14.1;Introduction;144 14.2;History;144 14.3;The NCGS Today;145 14.4;NCGS Substudies;146 14.5;NCGS Targeted Events;147 14.6;Importance of the NCGS: Conclusions;149 14.7;References;149 14.8;Appendix 1;150 15;Why we are Treating Children with Growth Hormone: Lessons from the French Registry;156 15.1;Summary;156 15.2;Introduction;156 15.3;Conclusion;162 15.4;Acknowledgments;162 15.5;References;162 16;Subject Index;166