Transforming growth factor ?1 (TGF?1) and progesterone regulate matrix metalloproteinases (MMP) in human endometrial stromal cells.

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 TGF?-responsive genes were also up-regulated in endometrium during this time, we tested the hypothesis that TGF?1 and progesterone regulate expression of MMP in human endometrial stromal cells (HESC).

Results

Treatment of HESC with TGF?1 resulted in marked increases in MMP2 and MMP11 mRNA and pro- and active MMP2 activity. Progesterone inhibited TGF?1-induced stimulation of MMP2 and MMP11 through its nuclear hormone receptors. Interestingly, TGF?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?1 has endogenous anti-progestational effects in HESC and that the opposing effects of progesterone and TGF?1 are important in regulation of matrix integrity in human endometrium.

SUBMITTER: Itoh H 

PROVIDER: S-EPMC3387423 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature