Plasminogen activator system: implications for mammary cell growth and involution

Several tissue remodeling events that require extracellular proteolysis are thought to be mediated by plasminogen activators that convert the inactive proenzyme plasminogen to active plasmin. The involvement of plasminogen activator in many biological phenomena reflects the ubiquitous presence of plasminogen and the ability of numerous cell types to synthesize plasminogen activator in a highly regulated manner. Increased plasmin and plasminogen activator in bovine milk are correlated with gradual involution (the declining phase of lactation). Treatment with bST prevented the increase in plasmin during gradual involution, indicating that bST interferes with conversion of plasminogen to plasmin. Concentrations of plasminogen activator in mammary tissue are high after cessation of milking. These results reinforce the association of the plasmin-plasminogen system with gradual involution postlactation. Recently, a role has been proposed for plasminogen activator in cell proliferation in several cellular systems. Insulin and IGF-I increased synthesis of urokinase plasminogen activator and enhanced proliferation of cultured bovine mammary epithelial cells. In contrast, phorbol myristate acetate, which increased expression of urokinase plasminogen activator mRNA by mammary epithelial and myoepithelial cells, stimulated proliferation of myoepithelial cells, but not epithelial cells. Thus, expression of plasminogen activator is not simply related to mitogenesis but is likely to serve multiple functions in bovine mammary epithelial cells.