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

Hiroko Itoh, A. Hari Kishore, Annika Lindqvist, David E. Rogers, R. Ann Word
In: The Journal of Clinical Endocrinology & Metabolism · 2012 · vol. 97(6) , pp. E888–E897 · doi:10.1210/jc.2011-3073 · PMID:22466340 · W2129840279
article OA: bronze CC0 ⤵ 12 in-corpus citations
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Transforming growth factor β1 increases MMP2 and MMP11 expression in human endometrial stromal cells, while progesterone inhibits this induction and decreases progesterone receptors.

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Abstract

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 TGFβ-responsive genes were also up-regulated in endometrium during this time, we tested the hypothesis that TGFβ1 and progesterone regulate expression of MMP in human endometrial stromal cells (HESC). RESULTS: Treatment of HESC with TGFβ1 resulted in marked increases in MMP2 and MMP11 mRNA and pro- and active MMP2 activity. Progesterone inhibited TGFβ1-induced stimulation of MMP2 and MMP11 through its nuclear hormone receptors. Interestingly, TGFβ1 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 TGFβ1 has endogenous anti-progestational effects in HESC and that the opposing effects of progesterone and TGFβ1 are important in regulation of matrix integrity in human endometrium.

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