title: Selective progesterone receptor modulator asoprisnil down-regulates collagen synthesis in cultured human uterine leiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer.
abstract: BACKGROUND
  A recent clinical trial demonstrated that selective progesterone receptor modulator asoprisnil is effective in reducing uterine leiomyoma volume. We investigated the effects of asoprisnil in vitro on the expression of the extracellular matrix (ECM)-remodeling enzymes and collagens in cultured leiomyoma and matching normal myometrial cells.
  
  
  METHODS
  The expression of extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMPs) and collagens were assessed by western blot analysis.
  
  
  RESULTS
  Untreated cultured leiomyoma cells had significantly lower EMMPRIN (P < 0.05), MMP-1 (P < 0.05) and membrane type 1-MMP (MT1-MMP) (P < 0.01) protein contents, but significantly higher TIMP-1 (P < 0.05), TIMP-2 (P < 0.01), type I (P < 0.05) and type III (P < 0.01) collagen protein contents compared with untreated cultured myometrial cells. Treatment with asoprisnil at concentrations > or =10(-7) M for 48 h significantly (P < 0.05) increased EMMPRIN, MMP-1 and MT1-MMP protein contents, and decreased TIMP-1 (P < 0.05), TIMP-2 (P < 0.01), type I (P < 0.01) and type III (P < 0.05 at 10(-7) M; P < 0.01 at 10(-6) M) collagen protein contents in cultured leiomyoma cells compared with control cultures. However, asoprisnil treatment did not affect the protein contents of ECM-remodeling enzymes and collagens in cultured myometrial cells.
  
  
  CONCLUSIONS
  These results suggest that asoprisnil may reduce collagen deposit in the ECM of cultured leiomyoma cells through decreasing collagen synthesis and enhancing the expression of EMMPRIN, MMPs and TIMPs without comparable effects on cultured myometrial cells.
authors.affiliation: Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Morikawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ohara
authors.forename: Qin
authors.initials: Q
authors.lastname: Xu
authors.forename: Koji
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Deborah A
authors.initials: DA
authors.lastname: DeManno
authors.forename: Kristof
authors.initials: K
authors.lastname: Chwalisz
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yoshida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Maruo
mesh_terms: D000328:Adult; D051926:Basigin / Q000378:metabolism*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis* / Q000187:drug effects; D015536:Down-Regulation; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D066298:In Vitro Techniques; D007889:Leiomyoma / Q000188:drug therapy / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D009215:Myometrium / Q000187:drug effects; D010091:Oximes / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000187:drug effects*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D015854:Up-Regulation; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000378:metabolism
chemical_list: D004963:Estrenes; D010091:Oximes; D011980:Receptors, Progesterone; D019714:Tissue Inhibitor of Metalloproteinases; D051926:Basigin; C488516:asoprisnil; D003094:Collagen; D020782:Matrix Metalloproteinases