Absorption of epidermal growth factor and insulin in rabbit renal proximal tubules

Epidermal growth factor (EGF), which stimulates the growth of a variety of tissues, was originally isolated from mouse submandibular glands. Human EGF (hEGF) has been isolated from the urine, and cDNA encoding for EGF has been isolated from the human kidney. Thus the kidney may represent an alternate source of EGF. Another potential explanation for the urinary content of EGF is a limited reabsorption of filtered EGF and/or a transtubular transport of EGF from the peritubular compartment to the lumen. Therefore, we exposed isolated and perfused rabbit proximal tubules to 125I-hEGF either in the perfusate or in the bath fluid. Luminal uptake of hEGF was compared with uptake of 125I-porcine insulin, which is known to be taken up with large efficiency. The results demonstrate that only 4% of the perfused 125I-hEGF load was taken up per millimeter of tubule length compared with 73% for insulin. Furthermore, hEGF is subject to a small transtubular transport from bath to lumen. Renal clearance of endogenous rabbit EGF was also measured and was comparable with that of creatinine. Thus in conclusion this study strongly suggests that filtered EGF to a large extent remains in the ultrafiltrate, unlike insulin, which is removed within the first few millimeters of proximal tubule. In addition filtered EGF in preurine is probably supplied by EGF transported intact across the proximal tubular epithelium.