The effect of epidermal growth factor on circulating levels of free and total IGF-I and IGF-binding proteins in adult rats.

Abstract

In neonatal rats, systemic administration of epidermal growth factor (EGF) results in reduced body weight gain and decreased levels of circulating IGF-I, which suggests that it be involved in the EGF-induced growth retardation. We investigated the effect of 4 weeks of EGF administration on circulating free and total IGF-I and IGF-binding proteins (IGFBPs) in adult rats treated with saline (controls), 30 (low dose group) and 150 (high dose group) microgram/kg/day EGF. Serum IGF-I was determined in ultrafiltrates (free) and acid-ethanol extracts (total), and serum IGFBPs using Western ligand blotting, which yielded four distinct molecular bands. The IGFBPs were tentatively identified as IGFBP-3 (a double band at 42 and 38 kDa), IGFBP-1 and/or IGFBP-2 (a single band at 30 kDa) and IGFBP-4 (a single band at 24 kDa). EGF administration did not change the body weight, tibia length, or liver, heart and lung weight. In contrast, serum total IGF-I and IGFBP-3 decreased dose-dependently: total IGF-I averaged 1470 +/- 100 micrograms/l (controls; mean +/- SEM), 1030 +/- 60 micrograms/l (low dose group; P < 0.005) and 760 +/- 40 micrograms/l (high dose group; P < 0.005), whereas differences between IGFBP-3 levels reached significance (P < 0.05) between controls and high dose rats, only. When compared to controls, levels of IGFBP-1 and/or IGFBP-2 were increased in the low dose group (P < 0.05), but unchanged in the high dose group. IGFBP-4 was unaffected by EGF. Free IGF-I averaged 74 +/- 6 micrograms/l in controls, and was reduced to 35 +/- 6 micrograms/l (low dose group; P < 0.005) and 57 +/- 5 micrograms/l (high dose group; P < 0.05). Free IGF-I was inversely correlated (r = -0.49, P < 0.05) with IGFBP-1 and/or IGFBP-2. We conclude that in adult rats prolonged EGF administration has a marked depressing effect on circulating total and free IGF-I. Nevertheless, we did not observe any somatic growth retardation.