Insulin-like growth factor binding protein-4 (IGFBP-4) and bone growth in childhood

IGFBP-4 is a 24kD protein, originally isolated from the conditioned medium of human bone cells, and has been implicated as a potent inhibitor of IGF action in vitro. To clarify its biological functions in human bone, I measured the serum concentration of IGFBP-4 from patients with endocrinologic disorders, using Western immunoblot.In normal children, IGFBP-4 increased with age. The serum IGFBP-4 levels of patients with GH deficiency and panhypopituitarism were lower than those of normal children. In addition, the serum levels of IGFBP-4 were also significantly lower in children with Turner's syndrome than in the age-matched normal children who were post pubertal. These findings suggest that GH and the sex steroid increase the production of serum IGFBP-4.Then, I examined the influence of GH on the serum level of of IGFBP-4. In the good responders to GH therapy, IGFBP-4 decreased rapidly during the first month, continued to decrease until the third month, and then increased slowly. On the contrary, in the poor responders to GH therapy, the IGFBP-4 level increased until the third month and then remained at a high level. The increased serum IGFBP-4 level may, at least in part, contribute to the low response to GH therapy in the poor responders.