60K gelatinase involved in mammary gland involution is regulated by β-oestradiol

AbstractCell matrix interactions are critical in the expression and maintenance of differentiated functions in mammary gland. Matrix metalloproteinases (MMPs), by acting on different matrix components, contribute to the remodelling of extracellular matrix. Of the three major gelatinases found in rat mammary gland at different stages of ontogeny, 60K gelatinase, a Ca2+ dependent neutral MMP, seems to be involved in involution, as it appears at the late stage of involution. Further investigations on its regulation by hormones which influence the mammary gland function were carried out. Administration of β-oestradiol caused the appearance of 60K gelatinase on the 2nd day of involution, while in untreated controls this activity was absent. On treatment of mammary epithelial cells of the 2nd day involuting tissue in culture with β-oestradiol, the 60K gelatinase activity appeared, while the untreated controls did not show the activity. The effect of β-oestradiol was studied further by metabolic labelling of the epithelial cells from the 2nd day involuting tissue. A concentration dependent increase in the amount of radiolabelled 60K gelatinase was found on treatment with β-oestradiol. The upregulation of the 60K gelatinase activity in vivo was also found by immunocytochemical staining of the β-oestradiol treated tissues. The effect of β-oestradiol appears to be specific for 60K as the activity of other gelatinases (130K and 68K) in the mammary gland were not affected. Furthermore, a drastic regression of the mammary gland as evidenced by histochemical analysis and a marked decrease in the milk protein production in β-oestradiol treated tissues indicated the onset of early involution. These results indicate that the 60K gelatinase which is upregulated during involution or on induction of early involution may play a key role in remodelling of extracellular matrix in mammary gland and further that this enzyme is subject to modulation by β-oestradiol