Insulin-like growth factor -I deficiency.
The insulin-like growth factor (IGF) system composed of two ligands, their receptors and regulatory proteins (acid-labile subunit and IGF-binding proteins) plays a central role in the regulation of growth and development in mammals. In addition to its key role in the stimulation of cellular proliferation and growth, IGF-I has important effects on carbohydrate, protein and bone metabolism. The molecular biology and physiology of the IGF system are complex, resulting in many potential mechanisms of IGF deficiency. Briefly, IGF-I deficiency may result from a primary defect in the IGF-I gene, its promoters, or may be secondary to a defect outside the gene itself. It may also result as a consequence of growth hormone (GH) deficiency, GH receptor/post-receptor abnormalities or abnormalities of the IGF-I receptor. The purpose of this presentation is to review the different types of IGF-I deficiency using the well-characterized clinical conditions with its associated biochemical and molecular defects. The clinical consequences in terms of phenotype-genotype, linear growth and body composition in patients with primary and secondary IGF deficiency will be presented, together with results from recombinant human (rh)IGF-I replacement therapy. Finally, as primary IGF-I deficiency is associated with insulin resistance, some of the metabolic actions of IGF-I will be briefly discussed.
Camacho-Hübner
C
C
Paediatric Endocrinology Section, Department of Endocrinology, St. Bartholomew's Hospital, London, UK. c.camacho-hubner@mds.qmw.ac.uk
Savage
M
M
D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use; D009154:Mutation / Q000502:physiology; D017451:Receptors, Somatomedin / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D013002:Somatomedins / Q000172:deficiency*
D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I