title: A potential mechanism of breakthrough bleeding associated with progestin: involvement in alteration of endometrial endothelial cells.
abstract: OBJECTIVE
  To explore the potential mechanism of breakthrough bleeding associated with progestin with in vitro methods.
  
  
  METHODS
  The isolation and culture of human endometrial endothelial cells (HEECs) was performed with the method established in our laboratory. The content and activity of urokinase-type plasminogen activator (uPA) and the content of plasminogen activator inhibitor-1 (PAI-1) in cell supernatants after incubated with different concentrations of progesterone (0-5 micromol/L) and 17beta-estradiol (0, 0.1, or 1 nmol/L) were measured by method of ELISA. Apoptosis rate of HEECs was measured by flow cytometry. Viable cell count was measured by MTT.
  
  
  RESULTS
  The increased level of progesterone (0.5-5 micromol/L) combined with 17beta-estradiol elevated content and activity of uPA while the production of PAI-1 remained unchanged. The apoptosis of HEECs was inhibited along with the increment of total viable cell counts at higher concentrations of progesterone with 17beta-estradiol.
  
  
  CONCLUSIONS
  The inhibition of apoptosis and increased content and activity of uPA may contribute to the occurrence of irregular bleeding associated with progestin use to some extent
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730.
authors.forename: Gui-hua
authors.initials: GH
authors.lastname: Sha
authors.forename: Shou-qing
authors.initials: SQ
authors.lastname: Lin
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004717:Endometrium / Q000166:cytology / Q000502:physiology*; D004727:Endothelium / Q000166:cytology / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D008796:Metrorrhagia / Q000209:etiology*; D011372:Progestins / Q000502:physiology*
chemical_list: D011372:Progestins; D004958:Estradiol