PATTERNS OF MATRIX METALLOPROTEINASE EXPRESSION IN CYCLING ENDOMETRIUM IMPLY DIFFERENTIAL FUNCTIONS AND REGULATION BY STEROID-HORMONES

Matrix metalloproteinases are a highly regulated family of enzymes, th at together can degrade most components of the extracellular matrix. T hese proteins are active in normal and pathological processes involvin g tissue remodeling; however, their sites of synthesis and specific ro les are poorly understood. Using in situ hybridization, we determined cellular distributions of matrix metalloproteinases and tissue inhibit or of metalloproteinase-1, an inhibitor of matrix metalloproteinases, in endometrium during the reproductive cycle. The mRNAs for all the me talloproteinases were detected in menstrual endometrium, but with diff erent tissue distributions. The mRNA for matrilysin was localized to e pithelium, while the others were detected in stromal cells. Only the t ranscripts for the 72-kD gelatinase and tissue inhibitor of metallopro teinases-1 were detected throughout the cycle. Transcripts for stromel ysin-2 and the 92-kD gelatinase were only detected in late secretory a nd menstrual endometrium, while those for matrilysin, the 72-kD gelati nase, and stromelysin-3 were also consistently detected in proliferati ve endometrium. These data indicate that matrix metalloproteinases are expressed in cell-type, tissue, and reproductive cycle-specific patte rns, consistent with regulation by steroid hormones, and with specific roles in the complex tissue growth and remodeling processes occurring in the endometrium during the reproductive cycle.