Time-dependent changes of levels of endogenous epidermal growth factor in submandibular glands, in kidneys, and in urine in rats during systemic treatment with EGF

Background: Exogenous EGF influences the levels of endogenous EGF different ly in the submandibular glands (SMG) and the kidneys. The aim of the presen t study was to examine the time-dependent changes in levels of endogenous E GF during 1-4 weeks of EGF treatment. Methods: Female rats were allocated i nto five groups receiving EGF subcutaneously (150 mu g/kg/day) for 0 (contr ols), 1, 2, 3 and 4 weeks prior to sacrifice at an age of 12 weeks. At the end of the study period, 24-h urine samples were collected. Results: The we ight of the SMG increased during EGF treatment (303+/-33 (controls), 359+/- 37 (1 week EGF, P < 0.01), 390+/-30 (4 weeks EGF, P < 0.001) (mg mean+/-S.D .)). The EGF content of the SMG was unchanged after 1 week but threefold de creased after 4 weeks of treatment, respectively. The expression of EGF mRN A was decreased after 1 and 4 weeks as assessed with in situ hybridization. The weight of the kidneys was unchanged after 1 week and increased after 4 weeks of treatment (828+/-105 mg (controls) vs. 935+/-44 mg (4 weeks EGF, P < 0.005)). The renal content and the urinary excretion of EGF were signif icantly increased by 20-30% only in the group treated for 4 weeks. Conclusi on: EGF treatment induces a time-dependent decrease in the EGF content in t he SMG most likely by reducing the biosynthesis of endogenous EGF. In contr ast, the EGF content in kidneys and in urine was unchanged after 1 week and increased after prolonged treatment. (C) 1998 Elsevier Science BN. All rig hts reserved.