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.
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.
Annunziata
Marta
M
Laboratory of Molecular and Cellular Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy.
Grande
Cristina
C
Scarlatti
Francesca
F
Deltetto
Francesco
F
Delpiano
Elena
E
Camanni
Marco
M
Ghigo
Ezio
E
Granata
Riccarda
R
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*
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