Up-regulation of insulin-like growth factor-I (IGF-I) receptor gene expression in patients with reduced serum IGF-I levels

Abstract

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.

Amniotic IGF-I supplementation of growth-restricted fetal sheep alters IGF-I and IGF receptor type 1 mRNA and protein levels in placental and fetal tissues

“…Our finding of up-regulation of mRNA for the IGF-I-1R in the gut in the IGF-I-treated fetuses, confirmed by increased protein expression in the jejunum, may be consistent with the reduced circulating IGF-I concentrations in these fetuses, as IGF-1R mRNA levels are reported to be inversely regulated by IGF-I (Werner et al 1989, Eshet et al 1993, Kind et al 1996, HernandezSanchez et al 1997). Since we found IGF-1R expression to be confined to the luminal aspect of the gut, where IGF-I concentrations were high, this might suggest that IGF-1R levels here are regulated by systemic factors rather than local factors.…”

Insulin-Like Growth Factor (IGF)-I, IGF-I Receptor, and IGF Binding Protein-3 Messenger Ribonucleic Acids and Protein in Corpora Lutea from ProstaglandinF2α-Treated Gilts1

“…It is possible that there is an up-regulation in IGF-IR in response to a decrease in available IGF-I, brought about by the increase in binding protein concentrations. In several past studies in other cell types, a decrease in available IGF-I up-regulated IGF-IR mRNA and protein expression [54][55][56]. The decrease in luteal IGF-IR protein seen in PGF 2␣ -treated vs. control animals on Day 9 may have been due to the degradation of the tissue as luteolysis progressed, and therefore is likely to have been a result of luteolysis rather than a possible cause.…”

Insulin and IGF‐1 Receptor Trafficking and Signalling

“…LeRoith: There are some studies showing the level of IGF-1 in the circulation ö high or low ö will a¡ect the gene expression of the IGF-1R (Eshet et al 1993) in addition to the internalization. The mechanism is not known but the mRNA was decreased with high IGF-1 and vice versa.…”

“…LDL and transferrin receptors, tyrosine kinase signalling receptors are not trapped in CCPs unless they have bound their ligand (Brown et al 1983, Carpentier 1994. They exhibit ligand occupancy-induced endocytosis which frequently requires the stimulation of the intrinsic tyrosine kinase (Carpentier 1993, 1994, Carpentier et al 1992, 1993, Welsh et al 1994, Wiley et al 1991. This activation triggers the translocation of the receptors from surface domains where they are maintained in an unoccupied state towards surface areas where CCPs are present (Carpentier & McClain 1995, Carpentier et al 1992, 1993, Hamer et al 1997.…”