title: Concurrent estrogen action was essential for maximal progestin effect in oral contraceptives.
abstract: OBJECTIVE
  To investigate the impact of estrogen contained in oral contraceptives (OCs) on the action of progestin on ovarian endometrioma epithelial cells.
  
  
  METHODS
  Experimental in vitro study and immunohistochemical analysis.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Patients who underwent surgery due to ovarian endometrioma.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  Telomerase-immortalized epithelial cells derived from ovarian endometrioma were treated with norethindorone (NET; 80 nmol/L) or levonorgestrel (LNG; 20 nmol/L) with or without 17β-ethynylestradiol (EE; 0.6 nmol/L) for 96 hours, and the cell growth was monitored. Estrogen receptor (ER) α, progesterone receptor (PR) A, and PRB expressions in clinical samples of ovarian endometrioma epithelial cells were analyzed with the use of immunohistochemistry.
  
  
  RESULTS
  NET or LNG effectively suppressed cell growth, and addition of EE significantly enhanced the growth suppression. This EE-mediated enhancement of cell growth suppression was observed only in cells that expressed ERα and therefore was ERα dependent. Western blot analysis revealed that expression of PRB was significantly induced by the addition of EE. Immunohistochemical analysis confirmed that ERα expression and PRB expression are significantly correlated, indicating that progestin-sensitive cells with PRB expression are predisposed to react with estrogen stimulation.
  
  
  CONCLUSIONS
  These findings suggest that EE contained in OCs plays a supportive role in progestin-induced growth inhibition of ovarian endometrioma epithelial cells. In the absence of estrogen priming, concurrent estrogen action was essential for rapid induction of PR to achieve maximal progestin effect.
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Bono
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. Electronic address: satoruky@med.kanazawa-u.ac.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kyo
authors.affiliation: Virology Division, National Cancer Center Research Institute, Tokyo, Japan. Electronic address: tkiyono@ncc.go.jp.
authors.forename: Tohru
authors.initials: T
authors.lastname: Kiyono
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Mizumoto
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Maida
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takakura
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D002461:Cell Line, Transformed; D003276:Contraceptives, Oral / Q000008:administration & dosage*; D004338:Drug Combinations; D004715:Endometriosis / Q000188:drug therapy / Q000378:metabolism; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D011372:Progestins / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D003276:Contraceptives, Oral; D004338:Drug Combinations; D004967:Estrogens; D011372:Progestins
keywords: Estrogen; oral contraceptive; ovarian endometrioma; progestin