Comparison of the mitogenic activity of human epidermal growth factor I-53 and epidermal growth factor I-48 in vitro and in vivo.
1. Epidermal growth factor is secreted into the gut lumen as a 53 amino acid peptide in vivo. Several preliminary studies have examined the clinical benefit of recombinant epidermal growth factor in intestinal disease, but there is inconsistency in the form of epidermal growth factor used (some using epidermal growth factor 1-48 and some epidermal growth factor 1-53), making comparisons difficult to evaluate. 2. We therefore examined the relative potency of recombinant epidermal growth factor 1-48 and epidermal growth factor 1-53 in stimulating [3H]thymidine uptake into primary rat hepatocytes at various doses in vitro and on various parameters of proliferation within the gastrointestinal tract when infused intravenously at 50 nmol day-1 kg-1 into rats receiving total parenteral nutrition. 3. Epidermal growth factor 1-53 was about twice as potent as epidermal growth factor 1-48 in its ability to stimulate [3H]thymidine incorporation into rat hepatocytes in vitro. In vivo studies supported this finding as, in both the small and large intestine, epidermal growth factor 1-53 caused about a 30% greater stimulation of intestinal growth than epidermal growth factor 1-48 (P < 0.001). 4. The 1-48 truncated form of epidermal growth factor is less active than the full-length molecule in vitro and in vivo. This must be borne in mind when comparing clinical trials that use different forms of recombinant epidermal growth factor.
Goodlad
R A
RA
Histopathology Unit, Imperial Cancer Research Fund, London, U.K.
Boulton
R
R
Playford
R J
RJ
D000818:Animals; D001681:Biological Assay; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D013936:Thymidine / Q000378:metabolism
D008934:Mitogens; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D013936:Thymidine