Transforming Growth Factor β1 (TGFβ1) and Progesterone Regulate Matrix Metalloproteinases (MMP) in Human Endometrial Stromal Cells

Context: Menstruation is preceded by progesterone withdrawal and endometrial matrix remodeling predominantly through induction of matrix metalloproteinases (MMP) and recruitment of invading neutrophils. Design: Using endometrial tissues from women during various phases of the menstrual cycle, we found that MMP2, MMP9, and MMP11 were up-regulated in the late secretory phase/premenstrual phase. Because TGF beta-responsive genes were also up-regulated in endometrium during this time, we tested the hypothesis that TGF beta 1 and progesterone regulate expression of MMP in human endometrial stromal cells (HESC). Results: Treatment of HESC with TGF beta 1 resulted in marked increases in MMP2 and MMP11 mRNA and pro- and active MMP2 activity. Progesterone inhibited TGF beta 1-induced stimulation of MMP2 and MMP11 through its nuclear hormone receptors. Interestingly, TGF beta 1 also decreased progesterone receptor (PR)-A and PR-B in HESC with a more pronounced effect on PR-A. Conclusions: These data support the hypothesis that TGF beta 1 has endogenous anti-progestational effects in HESC and that the opposing effects of progesterone and TGF beta 1 are important in regulation of matrix integrity in human endometrium. (J Clin Endocrinol Metab 97: E888-E897, 2012)