MODULATION OF IGF-I RECEPTORS BY EXOGENOUS HGH TREATMENT IN CONSTITUTIONALLY SHORT CHILDREN

OBJECTIVE To study the in-vivo regulation of IGF-I binding sites on er ythrocytes (RBC) following administration of growth hormone (hGH) to c onstitutionally short children. Recently, owing to biosynthetic techni ques, treatment with hGH has been administered not only to children wi th GH deficiency but also to children with constitutional growth delay and with familial short stature. PATIENTS AND DESIGN Growth hormone ( rhGH-Norditropin, Novo/Nordisk) was administered at a dose of 0.1 U/kg / day s.c. to 11 children with constitutional short stature. Before an d at 1-2 months after initiation of treatment IGF-I binding sites and serum IGF-I were determined. Erythrocytes were separated from whole bl ood by centrifugation over Ficoll Hypaque and used to assess IGF-I bin ding sites. RESULTS Serum IGF-I levels increased from 14.93 +/- 1.50 n mol/l (mean +/- SEM) to 30.29 +/- 2.32 nmol/l, with a mean difference of 15.36 +/- 2.21 (P = 0.00001). Concomitantly, the number of binding sites per cell decreased from 5.77 +/- 0.81 sites per cell (m +/- SEM) to 2.10 +/- 0.36; with a mean difference of -3.67 +/- 0.76 (P = 0.000 3). The dissociation constant (K-d) also decreased from 0.47 +/- 0.16 nM (m +/- SEM) to 0.10 +/- 0.02 with a mean difference of -0.37 +/- 0. 16 (P=0.02), indicating an increase in the affinity of the receptors. CONCLUSION Treatment of children with constitutional short stature wit h hGH raises the circulating IGF-I levels and down-regulates the IGF-I receptors; This study shows that IGF-I is capable of regulating ifs h omologous receptor concentrations in vivo and it is suggested that the measurement of IGF-I binding sites on RBC may be used for the diagnos is of subtle states of resistance to IGF-I.