High levels of matrix metalloproteinases regulate proliferation and hormone secretion in pituitary cells

Beside the digestion of the extracellular matrix during tumor invasion and metastasis, more recently, new functions for matrix metalloproteinases (MMP s) have been proposed. We studied the expression and function of these enzy mes in pituitary cells. We observed the activities of MMP-2 and MMP-9 toget her with expression of membrane-type MMP and tissue inhibitor of metallopro teinase-l in all types of human pituitary adenomas. We found surprisingly h igh levels of MMP activity and low levels of tissue inhibitor of metallopro teinases, indicating a high level of extracellular matrix-degrading activit y in pituitary adenomas. To examine the function of metalloproteinase activ ity in pituitary cells we used the synthetic MMP inhibitor batimastat. Thes e studies demonstrate that MMPs secreted by pituitary cells can release gro wth factors anchored to the extracellular matrix that, in turn, control pit uitary cell proliferation and hormone secretion. These results define a new additional mechanism for the control of pituitary hormone secretion and in dicate new potential therapeutic targets for pituitary adenomas.