title: The growth hormone-releasing hormone (GHRH) antagonist JV-1-36 inhibits proliferation and survival of human ectopic endometriotic stromal cells (ESCs) and the T HESC cell line.
abstract: OBJECTIVE
  To determine the effect of the GHRH antagonist JV-1-36 on proliferation and survival of primary ectopic human endometriotic stromal cells (ESCs) and the T HESC cell line.
  
  
  METHODS
  Prospective laboratory study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  22 women with endometriosis (aged 34.8+/-5.7 years) undergoing therapeutic laparoscopy.
  
  
  METHODS
  Eutopic (n=10) and ectopic (n=22) endometrial tissues were collected from women who underwent therapeutic laparoscopic surgery for endometriosis (stage III/IV).
  
  
  METHODS
  Expression of GHRH, GHRH receptor (GHRH-R) and GHRH-R splice variant (SV) 1 mRNA was determined by reverse-transcription polymerase chain reaction (RT-PCR). The ESC proliferation was assessed by 5-bromo-2-deoxyuridine incorporation, cell survival by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and Trypan blue assay. The T HESC survival was evaluated by MTT, cyclic adenosine monophosphate (cAMP) levels by ELISA, extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation by Western blot, and insulin-like growth factor (IGF)-2 mRNA by real-time PCR.
  
  
  RESULTS
  The ESCs and T HESCs, but not normal endometrial tissues, expressed GHRH-R mRNA; SV1 mRNA was determined in normal endometrial tissues, ESCs, and T HESCs; GHRH mRNAwas found in T HESCs; JV-1-36 inhibited ESC proliferation and ESC and T HESC survival. In T HESCs, JV-1-36 reduced cAMP production and ERK1/2 phosphorylation but had no effect on IGF-2 mRNA expression.
  
  
  CONCLUSIONS
  The GHRH antagonist JV-1-36 inhibits endometriotic cell proliferation and survival, suggesting that GHRH antagonist may represent promising tools for treatment of endometriosis.
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Annunziata
authors.forename: Cristina
authors.initials: C
authors.lastname: Grande
authors.forename: Francesca
authors.initials: F
authors.lastname: Scarlatti
authors.forename: Francesco
authors.initials: F
authors.lastname: Deltetto
authors.forename: Elena
authors.initials: E
authors.lastname: Delpiano
authors.forename: Marco
authors.initials: M
authors.lastname: Camanni
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.forename: Riccarda
authors.initials: R
authors.lastname: Granata
mesh_terms: D000328:Adult; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002828:Choristoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004353:Drug Evaluation, Preclinical; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D014591:Uterine Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D006727:Hormone Antagonists; C403071:JV 1-36; D020033:Protein Isoforms; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor