EPIDERMAL GROWTH-FACTOR STIMULATES INSULIN-LIKE GROWTH FACTOR-BINDINGPROTEIN-1 EXPRESSION IN THE NEONATAL RAT

Insulin-like growth factors (IGFs) and the IGF-binding proteins (IGFBP s) appear to be important in the regulation of perinatal growth. We ha ve shown previously that administration of epidermal growth factor (EG F) to newborn rat pups inhibits growth and decreases serum IGF-I conce ntrations. The experiments described here were designed to investigate the effect of EGF on the IGFBPs using ligand blots of serum and North ern analysis of hepatic RNA. EGF administration caused a rapid (within 2 h) 2-fold increase in the serum IGFBP-1 concentration. Hepatic IGFB P-1 mRNA increased even more rapidly, was increased at least 2-fold at 2 h, and remained elevated 4 h after EGF. The response to EGF was spe cific to IGFBP-1; IGFBP-2 hepatic mRNA content was not increased over the control value, and serum IGFBP-3 and -4 concentrations were not ch anged by ligand blot analysis. The IGFBP-1 response to EGF was most dr amatic in the first few days of life. Although EGF lowered circulating insulin levels, EGF stimulated IGFBP-1 secretion in the presence of e xogenously administered insulin. Thus, the increase in IGFBP-1 did not appear to be mediated by changes in serum insulin. These results demo nstrate that EGF increases serum IGFBP-1 concentrations, probably by s timulating synthesis. The association of decreased growth and increase d IGFBP-1 concentrations after EGF treatment suggests that elevated IG FBP-1 concentrations may restrict IGF bioactivity in the neonatal rat.