Glucocorticoids, Thyroid Hormone and Growth Hormone Interactions: Implications for the Growth Plate

Linear growth occurs during childhood and results from endochondral ossification in the growth plate. Prepubertal growth is primarily regulated by growth hormone (GH) and insulin-like growth factor (IGF)-I, with important contributions from glucocorticoids (GC) and thyroid hormone (T3). The somatomedin hypothesis proposed that GH stimulates hepatic IGF-I production, which then regulates growth via IGF-I receptor expressing chondrocytes in an endocrine fashion. Recent studies indicate that locally acting IGF-I is a key determinant of endochondral ossification and that GH, GC and T3 regulate expression of IGF-I and its receptor in the growth plate directly. Analysis of hormone imbalance during childhood and studies of genetically modified mice provide support for an important GH and IGF-I autocrine/paracrine pathway and for direct effects of GC and T3 during endochondral ossification. Thus, the epiphyseal growth plate is a key site for convergent hormone action that mediates the control of linear growth.