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 eryt hocytes (RBC) from 8 patients with Laron syndrome (LS), before and aft er IGF-I treatment (120-150 mug/kg/day s.c.). Basal fasting IGF-I aver aged 20.48 +/- 2.06 nmol/l (mean +/- S.E.M.) in the control group as c ompared to 4.72 +/- 0.84 nmol/l in the 8 LS patients (P = 0.000 1). Af ter 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 +/- 0.8 6 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 = 0.0 04 and -3.58 +/- 0.79, P = 0.002, respectively), values similar to tho se found in the control group. These data demonstrate that replacement treatment of LS patients with IGF-I down regulates its specific recep tors. We propose IGF-I binding to RBC as a test to determine the respo nsiveness of patients considered for long term IGF-I treatment.