The effect of epidermal growth factor on circulating levels of free and total IGF-I and IGF-binding proteins in adult rats.
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.
Frystyk
J
J
Institute of Experimental Clinical Research, Aarhus University Hospital, Denmark.
Vinter-Jensen
L
L
Skjaerbaek
C
C
Flyvbjerg
A
A
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D013006:Growth Hormone / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood* / Q000187:drug effects; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood / Q000187:drug effects; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood* / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone