title: Transforming growth factor β1 (TGFβ1) and progesterone regulate matrix metalloproteinases (MMP) in human endometrial stromal cells.
abstract: BACKGROUND
  Menstruation is preceded by progesterone withdrawal and endometrial matrix remodeling predominantly through induction of matrix metalloproteinases (MMP) and recruitment of invading neutrophils.
  
  
  METHODS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9032, USA.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Itoh
authors.forename: Annavarapu Hari
authors.initials: AH
authors.lastname: Kishore
authors.forename: Annika
authors.initials: A
authors.lastname: Lindqvist
authors.forename: David E
authors.initials: DE
authors.lastname: Rogers
authors.forename: R Ann
authors.initials: RA
authors.lastname: Word
mesh_terms: D000328:Adult; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D053507:Matrix Metalloproteinase 11 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008597:Menstrual Cycle / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D053773:Transforming Growth Factor beta1; D011374:Progesterone; C511771:MMP11 protein, human; D053507:Matrix Metalloproteinase 11; D020782:Matrix Metalloproteinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9