Endocrinology of growth.

Growth is a remarkably complex biological phenomenon, requiring the coordinated production of multiple hormones and growth factors. Human growth is characterized by several distinct features, including: (1) rapid growth in late gestation; (2) growth deceleration immediately following birth; (3) a prolonged childhood and a mid-childhood growth spurt; (4) a pubertal growth spurt; (5) relatively late attainment of adult height, and (6) minimal sexual dimorphism of adult stature. Secular changes in the height of humans probably reflect nutritional and environmental factors, rather than major genomic changes. While multiple hormones impact growth, the growth hormone (GH)-insulin-like growth factor (IGF) axis plays a central role in both intrauterine and postnatal growth. GH, after being secreted by the pituitary, binds to a transmembrane receptor and activates a postreceptor signaling cascade, ultimately leading to phosphorylation of signal transducer and activator of transcription (STAT) 5b. STAT5b transcriptionally regulates the genes for IGF-I and for key IGF-binding proteins. IGF-I, in turn, binds to the type 1 IGF receptor, resulting in chondrocyte proliferation and statural growth. IGF-deficient states may be divided into secondary forms, reflecting defects in GH production, and primary forms. Molecular defects of the GH-IGF axis have been identified in humans, with phenotypes that correspond to the specific genetic lesions. Therapy with GH or IGF-I can now be matched to specific defects in the GH-IGF axis.