title: Antiproliferative effects of the GnRH antagonist cetrorelix and of GnRH-II on human endometrial and ovarian cancer cells are not mediated through the GnRH type I receptor.
abstract: BACKGROUND
  The majority of human endometrial and ovarian cancer cell lines express receptors for GnRH. Their proliferation is time- and dose-dependently reduced by GnRH-I and its superagonistic analogues. Recently, we have demonstrated that, in human endometrial and ovarian cancer cell lines except for the ovarian cancer cell line EFO-27, the GnRH-I antagonist cetrorelix has antiproliferative effects comparable to those of GnRH-I agonists, indicating that the dichotomy between GnRH-I agonists and antagonists might not apply to the GnRH system in cancer cells. We were also able to show that the proliferation of human endometrial and ovarian cancer cells was dose- and time-dependently reduced by GnRH-II to a greater extent than by GnRH-I agonists.
  
  
  OBJECTIVE
  In this study we have assessed whether or not the antiproliferative effects of the GnRH-I antagonist cetrorelix in endometrial and ovarian cancer cells are mediated through the GnRH-I receptor.
  
  
  METHODS
  We analysed the antiproliferative effects of the GnRH-I agonist triptorelin, the GnRH-I antagonist cetrorelix and GnRH-II in a panel of endometrial and ovarian cancer cell lines expressing GnRH-I receptors, in the SK-OV-3 ovarian cancer cell line that does not express GnRH-I receptors, and in four GnRH-I receptor positive GnRH-I receptor knockout cell lines.
  
  
  RESULTS
  We found that, after knockout of the GnRH-I receptor, the antiproliferative effects of the GnRH-I agonist triptorelin were abrogated, whereas those of the GnRH-I antagonist cetrorelix and of GnRH-II persisted.
  
  
  CONCLUSIONS
  These data suggest that, in endometrial and ovarian cancer cells, the antiproliferative effects of cetrorelix and of GnRH-II are not mediated through the GnRH-I receptor.
authors.affiliation: Department of Gynecology and Obstetrics, Georg-August-University, D-37070 Göttingen, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Gründker
authors.forename: Lars
authors.initials: L
authors.lastname: Schlotawa
authors.forename: Volker
authors.initials: V
authors.lastname: Viereck
authors.forename: Nicola
authors.initials: N
authors.lastname: Eicke
authors.forename: Anika
authors.initials: A
authors.lastname: Horst
authors.forename: Britta
authors.initials: B
authors.lastname: Kairies
authors.forename: Günter
authors.initials: G
authors.lastname: Emons
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000502:physiology; D016889:Endometrial Neoplasms; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D016296:Mutagenesis; D010051:Ovarian Neoplasms; D011966:Receptors, LHRH / Q000235:genetics; D017329:Triptorelin Pamoate / Q000494:pharmacology
chemical_list: D018931:Antineoplastic Agents, Hormonal; C484844:GNRHR protein, human; C427484:GNRHR2 protein, human; D006727:Hormone Antagonists; D011966:Receptors, LHRH; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; C047717:LHRH, His(5)-Trp(7)-Tyr(8)-; C062876:cetrorelix