title: Expression of receptors for luteinizing hormone-releasing hormone in human ovarian and endometrial cancers: frequency, autoregulation, and correlation with direct antiproliferative activity of luteinizing hormone-releasing hormone analogues.
abstract: OBJECTIVE
  Several recent reports have demonstrated the expression of luteinizing hormone-releasing hormone receptors by human ovarian and endometrial cancers. Controversy persists on the relevance of this finding, in particular whether these receptors mediate direct antiproliferative effects of luteinizing hormone-releasing hormone analogues. We correlated the expression of luteinizing hormone-releasing hormone receptors by well-characterized ovarian and endometrial cancer cell lines with the ability of luteinizing hormone-releasing hormone analogues to reduce their proliferation and studied the autoregulation of luteinizing hormone-releasing hormone receptor expression by luteinizing hormone-releasing hormone agonist triptorelin and antagonist cetrorelix. The expression of luteinizing hormone-releasing hormone receptors was assessed in a series of specimens from primary ovarian and endometrial cancers.
  
  
  METHODS
  Luteinizing hormone-releasing hormone receptor expression was assessed by semiquantitative reverse transcriptase-polymerase chain reaction and radioligand binding assay. Antiproliferative effects were ascertained by proliferation assays in the absence or presence of luteinizing hormone-releasing hormone analogues.
  
  
  RESULTS
  Ovarian (4/6 cell lines) and endometrial (5/6 cell lines) cancer cell lines expressed luteinizing hormone-releasing hormone receptors. The proliferation of these luteinizing hormone-releasing hormone receptor-positive cell lines was dose- and time-dependently reduced by agonistic and antagonistic luteinizing hormone-releasing hormone analogues. Luteinizing hormone-releasing hormone receptor density was reduced to 80% of controls (control, 100 %; P <.001) by luteinizing hormone-releasing hormone analogues. Seventy percent of primary ovarian cancers and 83% of primary endometrial cancers expressed luteinizing hormone-releasing hormone receptors.
  
  
  CONCLUSIONS
  These findings suggest that luteinizing hormone-releasing hormone receptors that are expressed by human ovarian and endometrial cancer cell lines mediate direct antiproliferative effects of luteinizing hormone-releasing hormone analogues. Because most respective primary cancers expressed luteinizing hormone-releasing hormone receptors, these receptors might be used for novel antiproliferative therapeutic approaches and should be further evaluated.
authors.affiliation: Department of Obstetrics and Gynecology, Georg-August-University Göttingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Völker
authors.forename: Carsten
authors.initials: C
authors.lastname: Gründker
authors.forename: Oswald
authors.initials: O
authors.lastname: Schmidt
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Schulz
authors.forename: Günter
authors.initials: G
authors.lastname: Emons
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism*; D017329:Triptorelin Pamoate / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D011966:Receptors, LHRH; D017329:Triptorelin Pamoate