title: Effects of the levonorgestrel-releasing intrauterine system on proliferation and apoptosis in the endometrium.
abstract: BACKGROUND
  The levonorgestrel-releasing intrauterine system (LNg-IUS) has been shown to be effective in the management of menorrhagia. In order to evaluate the effects of LNg-IUS on endometrial proliferation and apoptosis, proliferating cell nuclear antigen (PCNA) expression, apoptosis, Fas and Bcl-2 protein expression in the endometrium were determined at the early proliferative phase of the menstrual cycle before and 3 months after LNg-IUS insertion.
  
  
  METHODS
  PCNA, Fas and Bcl-2 protein expression were analysed using an avidin-biotin immunoperoxidase method. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick-end labelling (TUNEL) method.
  
  
  RESULTS
  PCNA, immunolocalized both in the nuclei of endometrial glands and stroma was less abundant 3 months after insertion (P < 0.05). Bcl-2 protein, immunolocalized in the cytoplasm of endometrial glands but not in the stroma, became scanty 3 months after insertion. Fas antigen, immunolocalized only in endometrial glands before insertion, became prominent in both endometrial glands and stroma 3 months after insertion. The apoptosis-positive rate of the nuclei in both endometrial glands and stroma was significantly higher 3 months after insertion relative to that before insertion (P < 0.05).
  
  
  CONCLUSIONS
  LNg-IUS resulted in a decrease in endometrial proliferation and an increase in apoptosis in endometrial glands and stroma. The increase in apoptosis associated with increased Fas antigen expression and decreased Bcl-2 protein expression in the endometrium may be one of the underlying molecular mechanisms by which LNg-IUS insertion causes the atrophic change of the endometrium.
authors.affiliation: Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. maruo@kobe-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Maruo
authors.forename: J B
authors.initials: JB
authors.lastname: Laoag-Fernandez
authors.forename: P
authors.initials: P
authors.lastname: Pakarinen
authors.forename: H
authors.initials: H
authors.lastname: Murakoshi
authors.forename: I M
authors.initials: IM
authors.lastname: Spitz
authors.forename: E
authors.initials: E
authors.lastname: Johansson
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D016503:Drug Delivery Systems; D004715:Endometriosis / Q000209:etiology; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000627:therapeutic use; D008595:Menorrhagia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D013997:Time Factors; D019014:fas Receptor / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D016912:Levonorgestrel