Relaxin Increases Secretion of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 during Uterine and Cervical Growth and Remodeling in the Pig

Abstract

Matrix metalloproteinases are proteolytic enzymes that de- grade the extracellular matrix and are essential for tissue remodeling. Uterine and cervical growth require remodeling of structural barriers to cell invasion and matrix metallopro- teinase-2 and -9 degrade type IV collagen, the major compo- nent of basement membranes. Relaxin stimulates uterine and cervical growth and remodeling, which includes remodeling of support elements such as basement membranes. The ob- jective of this study was to determine whether relaxin alters the production and/or activity of matrix metalloproteinase-2 and -9 in the uterus or cervix of the pig. The growth-promoting effects of relaxin were elicited by administering relaxin to prepubertal gilts every 6 h for 54 h. The expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 was characterized by gel zymography, and proteins were quanti- fied by immunoblotting. Total enzyme activity was measured using matrix metalloproteinase-specific fluorescent sub- strate assays. In both uterine and cervical tissues, immuno- reactive matrix metalloproteinase-2 and matrix metallopro- teinase-9 protein expression was similar in relaxin-treated and control animals. However, tissue-associated gelatinase activity was attenuated by relaxin (P < 0.05). In contrast, relaxin significantly increased the secretion of active matrix metalloproteinase-2 and -9 protein into uterine fluid (P < 0.05). Given the importance of matrix metalloproteinases in extracellular matrix degradation, the observation that re- laxin promotes uterine secretion of matrix metalloprotein- ase-2 and -9 supports the concept that relaxin facilitates the growth and remodeling of reproductive tissues by increasing extracellular proteolysis in the pig reproductive tract. (Endocrinology 142: 3941-3949, 2001)