Epidermal growth factor and insulin-like growth factor I upregulate the expression of the epidermal growth factor system in rat liver

Background/Aim: Both epidermal growth factor and insulin-like growth factor I play a role in connection with the liver. In the present study, the poss ible interaction of these two growth factor systems was studied by investig ating the effect of epidermal growth factor or insulin-like growth factor I treatment on the expression of the epidermal growth factor receptor, and i ts activating ligands, transforming growth factor-alpha and epidermal growt h factor. Methods: Fifty-five male rats received no treatment, human recombinant epid ermal growth factor or human recombinant insulin-like growth factor I for e ither 3 or 7 days. The amount of epidermal growth factor receptor, transfor ming growth factor-alpha, and epidermal growth factor mRNA was quantitated by a calibrated user-friendly RT-PCR assay (CURT-PCR), and the expression o f transforming growth factor-alpha and epidermal growth factor peptides was quantitated by ELISA. Results: Control liver (n=16) contained a mean (+/-SD) value of 12.7+/-7.4x 10(-18) mol epidermal growth factor receptor mRNA, 3.8+/-2.0x10(-18) mol tr ansforming growth factor-alpha mRNA and 0.8+/-0.4x10(-18) mol epidermal gro wth factor mRNA per mu g total RNA and 9.8+/-1.6 fmol/mg protein epidermal growth factor and 144+/-22 fmol/mg protein transforming growth factor-alpha . Both epidermal growth factor and insulin-like growth factor I treatment i ncreased the expression of mRNA for transforming growth factor-alpha and ep idermal growth factor receptor, as well as the expression of transforming g rowth factor-alpha peptide. The level of epidermal growth factor receptor a nd transforming growth factor-alpha mRNA expression was found to correlate both in control and growth factor-treated animals, whereas the expression o f epidermal growth factor receptor and epidermal growth factor showed no co rrelation. Marked differences were seen upon activation of the two growth f actor systems, as epidermal growth factor, but not insulin-like growth fact or I treatment, increased the plasma concentration of urea and decreased th e concentration of insulin-like growth factor I and the liver enzymes, alan ine aminotransferase and alkaline phosphatase. Conclusion: Our results show that epidermal growth factor and insulin-like growth factor I, which belong to two different growth factor systems, both induce a correlated upregulation of transforming growth factor-alpha and ep idermal growth factor receptor mRNA in rat liver. Although marked differenc es were observed after treatment with either epidermal growth factor or ins ulin-like growth factor I on the liver as reflected in the plasma concentra tions of e.g. liver enzymes, a common motif in their action involves an upr egulation of the expression of the epidermal growth factor system.