title: GnRH II as a possible cytostatic regulator in the development of endometriosis.
abstract: BACKGROUND
  GnRH II is the second form of GnRH and is widely distributed in peripheral tissues of the female reproductive tract as well as in the central nervous system. In the present study, we studied the possible implication of GnRH II in endometriosis.
  
  
  METHODS
  Effects of GnRH II on 5-bromo-2'-deoxyuridine (BrdU) uptake by cultured endometriotic stromal cells were examined. Effects of GnRH II on interleukin (IL)-1beta-induced expression of cyclooxygenase (COX)-2 and IL-8 were also studied. mRNA levels of GnRH I, GnRH II, type I GnRH receptor and type II GnRH receptor were determined by real-time quantitative RT-PCR in endometrial tissues of women with or without endometriosis and in endometriotic tissues.
  
  
  RESULTS
  GnRH II dose-dependently suppressed BrdU uptake by endometrial stromal cells. Treatment with IL-1beta markedly increased mRNA levels of COX-2 and IL-8 in endometrial stromal cells and IL-8 protein secretion by these cells, while these increments were significantly suppressed by supplementation with GnRH II. The mRNA levels of GnRH II were lower in endometrial and endometriotic tissues of women with endometriosis than in endometrial tissues of women without endometriosis, both in the proliferative phase and the secretory phase. In addition, as for GnRH I, type I GnRH receptor and type II GnRH receptor, the mRNA levels were lower in endometrial tissues of women with endometriosis than in those without endometriosis in the secretory phase.
  
  
  CONCLUSIONS
  In the light of the demonstrated antiproliferative and anti-inflammatory effects of GnRH II on endometrial stromal cells, the lower expression of GnRH II in eutopic and ectopic endometrium of women with endometriosis suggests that endogenous GnRH II-mediated cytostatic regulation may be impaired in the development of endometriosis.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Morimoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Osuga
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yano
authors.forename: Yuri
authors.initials: Y
authors.lastname: Takemura
authors.forename: Miyuki
authors.initials: M
authors.lastname: Harada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hirata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hirota
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshino
authors.forename: Kaori
authors.initials: K
authors.lastname: Koga
authors.forename: Koji
authors.initials: K
authors.lastname: Kugu
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taketani
mesh_terms: D000328:Adult; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004715:Endometriosis / Q000139:chemically induced*; D004717:Endometrium / Q000166:cytology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011966:Receptors, LHRH / Q000096:biosynthesis; D017154:Stromal Cells / Q000187:drug effects / Q000502:physiology
chemical_list: D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D051546:Cyclooxygenase 2; D001973:Bromodeoxyuridine