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

• Published in: The journal of clinical endocrinology and metabolism Vol. 85; no. 1; pp. 263 - 269
• Main Authors: PAEZ PEREDA, M, LEDDA, M. F, STALLA, G. K, GOLDBERG, V, CHERVIN, A, CARRIZO, G, MOLINA, H, MÜLLER, A, RENNER, U, PODHAJCER, O, ARZT, E
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 2000
• Subjects: Adenoma - metabolism; Adenoma - pathology; Adult; Aged; Aged, 80 and over; Animals; Biological and medical sciences; Blotting, Northern; Cell Division - drug effects; Cell Division - physiology; Endocrinopathies; Female; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Male; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 9 - biosynthesis; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases - metabolism; Medical sciences; Middle Aged; Neoplastic Stem Cells; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Phenylalanine - analogs & derivatives; Phenylalanine - pharmacology; Pituitary Gland - cytology; Pituitary Gland - drug effects; Pituitary Gland - metabolism; Pituitary Hormones - biosynthesis; Pituitary Neoplasms - metabolism; Pituitary Neoplasms - pathology; Protease Inhibitors - pharmacology; Rats; Thiophenes - pharmacology; Tissue Inhibitor of Metalloproteinase-1 - antagonists & inhibitors; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Tissue Inhibitor of Metalloproteinase-2 - antagonists & inhibitors; Tissue Inhibitor of Metalloproteinase-2 - metabolism; Tropical medicine; Tumor Cells, Cultured; South America; Argentina; America; Endocrinopathy; Human; Cell proliferation; Enzyme; Enzyme inhibitor; Metalloendopeptidases; Adenoma; In vitro; Biological activity; Gelatinase B; Gelatinase A; Endocrine secretion; Peptidases; Enzymatic activity; Pituitary diseases; Hydrolases; Pituitary gland; Benign neoplasm; Comparative study
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.85.1.263

Beside the digestion of the extracellular matrix during tumor invasion and metastasis, more recently, new functions for matrix metalloproteinases (MMPs) have been proposed. We studied the expression and function of these enzymes in pituitary cells. We observed the activities of MMP-2 and MMP-9 together with expression of membrane-type MMP and tissue inhibitor of metalloproteinase-1 in all types of human pituitary adenomas. We found surprisingly high levels of MMP activity and low levels of tissue inhibitor of metalloproteinases, indicating a high level of extracellular matrix-degrading activity in pituitary adenomas. To examine the function of metalloproteinase activity in pituitary cells we used the synthetic MMP inhibitor batimastat. These studies demonstrate that MMPs secreted by pituitary cells can release growth factors anchored to the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. These results define a new additional mechanism for the control of pituitary hormone secretion and indicate new potential therapeutic targets for pituitary adenomas.