PMID- 22466340 OWN - NLM STAT- MEDLINE DCOM- 20120815 LR - 20240318 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 97 IP - 6 DP - 2012 Jun TI - Transforming growth factor beta1 (TGFbeta1) and progesterone regulate matrix metalloproteinases (MMP) in human endometrial stromal cells. PG - E888-97 LID - 10.1210/jc.2011-3073 [doi] AB - 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 TGFbeta-responsive genes were also up-regulated in endometrium during this time, we tested the hypothesis that TGFbeta1 and progesterone regulate expression of MMP in human endometrial stromal cells (HESC). RESULTS: Treatment of HESC with TGFbeta1 resulted in marked increases in MMP2 and MMP11 mRNA and pro- and active MMP2 activity. Progesterone inhibited TGFbeta1-induced stimulation of MMP2 and MMP11 through its nuclear hormone receptors. Interestingly, TGFbeta1 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 TGFbeta1 has endogenous anti-progestational effects in HESC and that the opposing effects of progesterone and TGFbeta1 are important in regulation of matrix integrity in human endometrium. FAU - Itoh, Hiroko AU - Itoh H AD - Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9032, USA. FAU - Kishore, Annavarapu Hari AU - Kishore AH FAU - Lindqvist, Annika AU - Lindqvist A FAU - Rogers, David E AU - Rogers DE FAU - Word, R Ann AU - Word RA LA - eng GR - P01 HD011149/HD/NICHD NIH HHS/United States GR - HD11149/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120330 PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Transforming Growth Factor beta1) RN - 4G7DS2Q64Y (Progesterone) RN - EC 3.4.24.- (MMP11 protein, human) RN - EC 3.4.24.- (Matrix Metalloproteinase 11) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.4.24.24 (MMP2 protein, human) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Adult MH - Endometrium/cytology/*metabolism MH - Female MH - Gene Expression Regulation, Enzymologic/drug effects/physiology MH - Humans MH - In Vitro Techniques MH - Matrix Metalloproteinase 11/genetics/metabolism MH - Matrix Metalloproteinase 2/genetics/metabolism MH - Matrix Metalloproteinase 9/genetics/metabolism MH - Matrix Metalloproteinases/genetics/*metabolism MH - Menstrual Cycle/*metabolism/physiology MH - Middle Aged MH - Progesterone/*metabolism/pharmacology MH - Stromal Cells/cytology/drug effects/*metabolism MH - Transforming Growth Factor beta1/*metabolism/pharmacology PMC - PMC3387423 EDAT- 2012/04/03 06:00 MHDA- 2012/08/16 06:00 PMCR- 2013/06/01 CRDT- 2012/04/03 06:00 PHST- 2012/04/03 06:00 [entrez] PHST- 2012/04/03 06:00 [pubmed] PHST- 2012/08/16 06:00 [medline] PHST- 2013/06/01 00:00 [pmc-release] AID - jc.2011-3073 [pii] AID - 11-3073 [pii] AID - 10.1210/jc.2011-3073 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2012 Jun;97(6):E888-97. doi: 10.1210/jc.2011-3073. Epub 2012 Mar 30.