Kinetics of transfer of 125I-labelled epidermal growth factor from blood into mammary secretions of goats.

125I-Labelled mouse epidermal growth factor (125I-EGF) was transferred intact and undegraded from circulating blood into milk in conscious lactating goats. Greater than 90% of the total radioactivity present in milk from the infused gland was in the aqueous phase and more than 72% was acid-precipitable. This radiolabelled material co-eluted with authentic EGF through gel filtration and was immunoprecipitable by a specific rabbit anti-mouse EGF immunoglobulin. Mammary uptake of 125I-EGF infused into mammary arterial blood (close-arterial infusion) for 1 h varied from 20 to 83% at different stages of the reproductive cycle. Only 0.5-2.9% of the infused 125I-EGF was transferred into milk during the first 3 h after the start of the infusion, which represents 0.7-6.3% of mammary uptake of EGF. The kinetics of transfer of 125I-EGF were followed in two lactating goats. Radioactivity reached peak levels in milk about 120 min after the start of a 1 h close-arterial infusion into the mammary gland, with an initial lag of about 30 min when little transfer occurred. Transfer was slower in two non-lactating goats with maximal levels of activity in milk being reached after about 180 min. The results are consistent with a transcellular transfer, whereby the factor is bound to receptors on the baso-lateral membrane, internalized by epithelial cells and subsequently secreted across the apical membrane into the alveolar lumen. The low level of degraded labelled EGF in milk (and mammary vein blood) suggests a modification of the normal pathway of EGF degradation such that the delivery of internalized factor to lysosomes is avoided.