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. I-125-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 (K(d)=0.49+/-0.05 nm), than erythrocytes from controls (2.0+/-0.4 sites/cell; K(d)= 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.