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

• Published in: The journal of clinical endocrinology and metabolism Vol. 97; no. 6; pp. E888 - E897
• Main Authors: Itoh, Hiroko, Kishore, Annavarapu Hari, Lindqvist, Annika, Rogers, David E, Word, R. Ann
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.06.2012; Copyright by The Endocrine Society
• Subjects: Adult; Endometrium - cytology; Endometrium - metabolism; Female; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Enzymologic - physiology; Hot Topics in Translational Endocrinology; Humans; In Vitro Techniques; Matrix Metalloproteinase 11 - genetics; Matrix Metalloproteinase 11 - metabolism; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinases - genetics; Matrix Metalloproteinases - metabolism; Menstrual Cycle - metabolism; Menstrual Cycle - physiology; Middle Aged; Progesterone - metabolism; Progesterone - pharmacology; Stromal Cells - cytology; Stromal Cells - drug effects; Stromal Cells - metabolism; Transforming Growth Factor beta1 - metabolism; Transforming Growth Factor beta1 - pharmacology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2011-3073

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.