title: Progestins inhibit estradiol-induced vascular endothelial growth factor and stromal cell-derived factor 1 in human endometrial stromal cells.
abstract: OBJECTIVE
  To investigate whether 17β-estradiol (E(2)) and progestins exert direct effects on vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1/CXCL12) in human endometrial stromal cells (ESCs) and thereby to clarify the regulatory function of these local angiogenic factors in the endometrium.
  
  
  METHODS
  In vitro experiment.
  
  
  METHODS
  Research laboratory at Kansai Medical University.
  
  
  METHODS
  Fourteen patients undergoing hysterectomy for benign reasons.
  
  
  METHODS
  ESCs were cultured with E(2) and/or various clinically relevant progestins (medroxyprogesterone acetate [MPA], norethisterone [NET], levonorgestrel [LNG], dienogest [DNG], and progesterone [P]).
  
  
  METHODS
  The mRNA levels and production of VEGF and SDF-1 were assessed by real-time reverse-transcription polymerase chain reaction and ELISA, respectively.
  
  
  RESULTS
  E(2) significantly induced the mRNA levels and protein production of VEGF and SDF-1 in ESCs. MPA could antagonize the E(2)-stimulated effects in a time- and dose-dependent manner, and this effect could be reversed by RU-486 (P receptor antagonist). All of the progestins (MPA, NET, LNG, and DNG; 10(-9) to 10(-7) mol/L) attenuated E(2)-induced VEGF and SDF-1 production, whereas P showed these inhibitory effects only when present in a high concentration (10(-7) mol/L).
  
  
  CONCLUSIONS
  Progestins have inhibitory effects on E(2)-induced VEGF and SDF-1 in ESCs. These results may indicate a potential mechanism for action of the female sex steroids in the human endometrium that can be helpful for various clinical applications.
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan. hokada@hirakata.kmu.ac.jp
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Okada
authors.forename: Rika
authors.initials: R
authors.lastname: Okamoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: Shoko
authors.initials: S
authors.lastname: Tsuji
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yasuda
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kanzaki
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000502:physiology*; D004347:Drug Interactions; D004717:Endometrium / Q000166:cytology* / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D011372:Progestins / Q000494:pharmacology* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology*
chemical_list: D054377:Chemokine CXCL12; D011372:Progestins; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004958:Estradiol