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Kathryn Cox1 , Kathy Sharpe-Timms1 *, Noriko Kamiya2 , Manish Saraf2 , Kathleen Donnelly2 , Asgerally Fazleabas2
Departments of Biochemistry and Ob/Gyn, University of Missouri-Columbia, Missouri 1
Department of Ob/Gyn, University of Illinois-Chicago, Illinois 2
Matrix metalloproteinases (MMPs) have been implicated in endometrial remodeling. In humans and rhesus monkeys, endometrial MMP-3 peaks during progesterone (P) withdrawal at the end of the menstrual cycle. This in vivo study evaluated MMP-3 mRNA expression and protein synthesis in endometrial tissue and uterine flushings from normally cycling (n=7) and ovariectomized, estradiol (E) or P treated (OVX/EP; n=5) baboons. Additional animals (n=4) were treated with the anti-progestin ZK 137.316 for 9 days beginning at the LH surge. Total endometrial RNA (10 µg) was hybridized to a human MMP-3 probe (nucleotides 702-1286). Uterine fluid MMP-3 was analyzed by Western analysis using anti-human MMP-3 antibody. Densitometric analysis was performed. In normally cycling animals, minimal MMP-3 message or protein was found in the proliferative or secretory phases. This concurs with previous reports suggesting MMP-3 is not regulated by E. During early menses, MMP-3 message increased 10-fold yet, only a slight increase in MMP-3 protein was seen in uterine fluid. Anti-progestin treatment resulted in little change in MMP-3 message compared to the mid-secretory phase. OVX/EP baboons showed analogous results to normally cycling animals. In conclusion: 1) endometrial MMP-3 expression is similar in baboons, humans and rhesus monkeys; 2) similar patterns of MMP-3 expression in normally cycling and OVX/EP animals support this model for future studies; and 3) P does not directly suppress stromal MMP-3 expression, in contrast to P suppression of glandular epithelial MMP-7, suggesting differential regulation of MMP gene expression in the two major endometrial cell types in the baboon. These studies support the hypothesis that local events, as opposed to direct P supression, play a preferential role in regulating endometrial MMP-3 expression. (NIH 29026 to KST and NIH 29964 to ATF)
This abstract is being presented on Tuesday, August 3 at 5:15 PM at Todd 130.