Relaxin increases secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9 during uterine and cervical growth and remodeling in the pig

Matrix metalloproteinases are proteolytic enzymes that degrade the extracel lular matrix and are essential for tissue remodeling. Uterine and cervical growth require remodeling of structural barriers to cell invasion and matri x metalloproteinase-2 and -9 degrade type IV collagen, the major component of basement membranes. Relaxin stimulates uterine and cervical growth and r emodeling, which includes remodeling of support elements such as basement m embranes. The objective of this study was to determine whether relaxin alte rs the production and/or activity of matrix metalloproteinase-2 and -9 in t he uterus or cervix of the pig. The growth-promoting effects of relaxin wer e 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 quantified by imm unoblotting. Total enzyme activity was measured using matrix metalloprotein ase-specific fluorescent substrate assays. In both uterine and cervical tis sues, immunoreactive matrix metalloproteinase-2 and matrix metalloproteinas e-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 act ive 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 relaxin promotes uterine secretion of ma trix metalloproteinase-2 and -9 supports the concept that relaxin facilitat es the growth and remodeling of reproductive tissues by increasing extracel lular proteolysis in the pig reproductive tract.