Trauma, especially of the submandibular glands, causes release of epidermal growth factor into bloodstream in mice.

Submandibular glands in mice were traumatized by handling and then removed. Immunoreactive epidermal growth factor (EGF) in serum increased after 5 min and continued to increase, reaching at 1 h a peak of 50-fold normal in males and twice normal in females. If after traumatization the glands were repositioned with their blood supply intact, maximal increase of serum EGF at 1 h was 190-fold control values in males and 2-fold in females. In male mice, incision of abdominal wall skin led to a 15-fold increase of EGF in the serum; this rise was absent 3 days after sialoadenoectomy. After traumatization, repositioned submandibular glands lost 80% of their EGF; after the abdominal wall incision, only 30%. Following removal of submandibular glands, decrease of EGF level in serum was very slow: to 60% of the initial value after 3 days and to 40% after 10 days. By the HPLC characteristics, immunoreactive EGF in control serum and at its peak were indistinguishable. Urinary excretion of EGF was significantly elevated only when its serum level was 190-fold normal. We conclude that traumatized submandibular glands discharge into circulation a large part of their stored EGF. A similar but much less pronounced process takes place after abdominal skin incision. The presence of EGF in serum after its slow decline in sialoadenoectomized mice shows that a fraction of circulating EGF may recirculate prolonging its apparent half-life.