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 erythrocytes (RBC) from 8 patients with Laron syndrome (LS), before and after IGF-I treatment (120-150 micrograms/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.
Eshet
R
R
Endocrine and Diabetes Research Unit, Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University.
Klinger
B
B
Silbergeld
A
A
Laron
Z
Z
D000293:Adolescent; D000328:Adult; D001665:Binding Sites; D002648:Child; D002675:Child, Preschool; D004392:Dwarfism / Q000097:blood* / Q000628:therapy*; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism* / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use; D012044:Regression Analysis
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1