Up-regulation of insulin-like growth factor-I (IGF-I) receptor gene expression in patients with reduced serum IGF-I levels.
We have analysed the expression of the IGF-I receptor gene in lymphocytes of patients with low levels of circulating IGF-I (four patients with isolated GH deficiency (IGHD) and one Laron-type dwarf (LTD)) in comparison with a control group exhibiting normal serum IGF-I levels and endocrine profiles. 125I-Labelled IGF-I binding assays were performed on erythrocytes to determine the number of IGF-I binding sites per cell and their dissociation constants. Erythrocytes from patients with IGHD or LTD contained significantly (P = 0.002) more receptors per cell (10.9 +/- 3.1 binding sites/cell), with a reduced affinity (Kd = 0.49 +/- 0.05 nM), than erythrocytes from controls (2.0 +/- 0.4 sites/cell; Kd = 0.14 nM). The levels of IGF-I receptor mRNA in circulating lymphocytes were determined by an RNA template-specific reverse transcription/polymerase chain reaction method. There was a statistically significant increase in IGF-I receptor mRNA levels in lymphocytes from patients with LTD or IGHD when compared with controls (3108.1 +/- 775.9 vs 576.0 +/- 465.7 arbitrary units, P = 0.006). The increased level of IGF-I binding due to increased IGF-I receptor gene expression may represent a compensatory up-regulation process activated in response to the low levels of IGF-I in the circulation of patients with LTD or IGHD.
Eshet
R
R
Institute of Pediatric and Adolescent Endocrinology, Beilinson Medical Center, Petach Tikva, Israel.
Werner
H
H
Klinger
B
B
Silbergeld
A
A
Laron
Z
Z
LeRoith
D
D
Roberts
C T
CT
D001483:Base Sequence; D002648:Child; D004247:DNA; D004392:Dwarfism / Q000097:blood*; D013006:Growth Hormone / Q000172:deficiency; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011863:Radioimmunoassay; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015854:Up-Regulation
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D004247:DNA; D017526:Receptor, IGF Type 1