Modulation of insulin like growth factor I (IGF-I) binding sites on erythrocytes by IGF-I treatment in patients with Laron syndrome (LS)

The in vivo regulation of IGF-I binding sites was evaluated using erythocytes (RBC) from 8 patients with Laron syndrome (LS), before and after IGF-I treatment (120-150 μg/kg/day s.c.). Basal fasting IGF-I averaged 20.48 ± 2.06 nmol/l (mean ± S.E.M.) in the control group as compared to 4.72 ± 0.84 nmol/l in the 8 LS patients (P = 0.0001). After 1 week of IGF-I treatment serum IGF-I levels increased to 6.53 ± 1.58 nmol/l (a mean difference of 1.81 ± 0.95, P = 0.05) and after 1 month of treatment to 14.37 ± 4.56 nmol/l (a mean difference of 9.37 ± 4.42, P = 0.03). Concomitantly, we found a significant decrease in the number of high affinity IGF-I binding sites, from 5.74 ± 0.86 sites/cell (mean ± S.E.M.) in the non-treated state to 2.29 ± 0.64 sites/cell and 2.17 ± 0.53 sites/cell after 1 week and 1 month of treatment, respectively (a mean difference of -3.44 ± 0.94, P = 0.004 and -3.58 ± 0.79, P = 0.002, respectively), values similar to those found in the control group. These data demonstrate that replacement treatment of LS patients with IGF-I down regulates its specific receptors. We propose IGF-I binding to RBC as a test to determine the responsiveness of patients considered for long term IGF-I treatment.