Stress down regulates milk yield in cows by plasmin induced beta-casein product that blocks K+ channels on the apical membranes

Stress and stress related hormones such as glucocorticoids inhibit lactation in cows. In the present study we propose a novel mechanism connecting stress with plasminogen-plasmin system (PPS) (an enzymatic mechanism in milk, which leads to the breakdown of the major milk protein casein). We show that stress activates the PPS leading to an increase in plasmin activity, and that a distinct plasmin-induced beta-casein breakdown product (fraction 1-28) is a potent blocker of potassium channels in mammary epithelia apical membranes. The reduction in milk production due to dehydration stress or glucocorticoid (dexamethsone) was correlated with the activities of plasmin and channel blocking activity in the milk of the tested cows. The notion that the axis Stress-PPS-beta-casein fraction 1-28 is responsible for the reduction in milk yield is supported by the results of experiments showing that injecting solution composed of casein digest enriched with beta-casein fraction 1-28 to the udder lumen leads to a transient reduction in milk production. Furthermore, injecting a pure beta-casein fraction 1-28 to the udder lumen of goat's lead also to a transient reduction in milk production with kinetics that was similar to the kinetics observed in cows.