Transforming growth factor β1 (TGFβ1) and progesterone regulate matrix metalloproteinases (MMP) in human endometrial stromal cells

Hiroko Itoh, A. Hari Kishore, Annavarapu Hari Kishore, Annika Lindqvist, David E. Rogers, R. Ann Word
The Journal of clinical endocrinology and metabolism · 2012 · vol. 97(6) , pp. E888–E897 · doi:10.1210/jc.2011-3073 · PMID:22466340 · PMC3387423 · W2129840279
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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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MeSH descriptors

Endometrium Matrix Metalloproteinases Menstrual Cycle Progesterone Stromal Cells Transforming Growth Factor beta1 Adult Endometrium Endometrium Female Gene Expression Regulation, Enzymologic Gene Expression Regulation, Enzymologic Gene Expression Regulation, Enzymologic Humans In Vitro Techniques Matrix Metalloproteinase 11 Matrix Metalloproteinase 11 Matrix Metalloproteinase 11 Matrix Metalloproteinase 2 Matrix Metalloproteinase 2

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