Infusion of epidermal growth factor in mice: organ distribution and urinary excretion

Anesthetized mice were infused into the tail vein with 7.5% mannitol in saline (0.1 ml/min for 60 min) alone or with EGF at 0.5 microgram/min. Urine was collected every 10 min starting 20 min after the beginning of the infusion and ending 20 min after its termination. EGF concentration in the serum of mice infused with EGF increased from the baseline level of 0.6 +/- 0.4 to 70.7 +/- 16.0 ng/ml at 80 min. Total excretion of EGF for 80 min was 117 +/- 49 ng with mannitol alone and 1916 +/- 420 ng (6.4% of the EGF infused) after mannitol with EGF. Serum and urine EGF was indistinguishable from the native mouse EGF by its radioimmunoassay and HPLC characteristics. Intact labeled EGF was also found in urine when mice were infused with 125I-EGF (1 x 10(6) cpm/ml) in mannitol. After 5 min infusion with 125I-EGF (6 x 10(6) cpm/ml in saline), more than 80% of the label was found in the liver and kidneys and more than 90% of it was intact EGF. However, 30 min after infusion more than 95% of the labeled EGF was degraded. We conclude that at least part of the urinary EGF in mice originates in blood and that liver and kidneys are the main organs of EGF degradation.