title: Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells.
abstract: BACKGROUND
  This study was conducted to evaluate the effects of graded concentrations (10(-8), 10(-7) and 10(-6) M) of progesterone receptor (PR) modulator CDB-2914 on the protein contents of PR, of vascular endothelial growth factor (VEGF), adrenomedullin (ADM) and their receptors in cultured human uterine leiomyoma and matching myometrial cells.
  
  
  METHODS
  PR-A, PR-B, VEGF-A, VEGF-B, VEGF receptor (VEGFR)-1, VEGFR-2, ADM and ADM receptor (ADMR) contents were assessed by Western blot analysis.
  
  
  RESULTS
  Treatment with 100 ng/ml progesterone increased VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells and normal myometrial cells. The concomitant treatment with 10(-6) M CDB-2914 significantly decreased the progesterone-induced VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment alone decreased VEGFR-1, VEGFR-2 and ADMR contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment increased PR-A and decreased PR-B contents in cultured leiomyoma cells in a dose-dependent manner compared with untreated cultures, whereas no significant changes in PR isoform contents were observed in normal myometrial cells.
  
  
  CONCLUSIONS
  These results suggest that CDB-2914 down-regulates VEGF, ADM and their receptor contents and modulates PR isoform contents in cultured leiomyoma cells in a cell-type-specific manner.
authors.affiliation: Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Qin
authors.initials: Q
authors.lastname: Xu
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ohara
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Morikawa
authors.forename: Regine
authors.initials: R
authors.lastname: Sitruk-Ware
authors.forename: Elof D B
authors.initials: ED
authors.lastname: Johansson
authors.forename: Takeshi
authors.initials: T
authors.lastname: Maruo
mesh_terms: D053607:Adrenomedullin / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism; D009649:Norpregnadienes / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000096:biosynthesis* / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D009649:Norpregnadienes; D011980:Receptors, Progesterone; D042461:Vascular Endothelial Growth Factor A; C097314:progesterone receptor B; D053607:Adrenomedullin; C094854:ulipristal