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

Annunziata M, Marta Annunziata, Grande C, Cristina Grande, Scarlatti F, Francesca Scarlatti, Francesco Deltetto, Deltetto F, Elena Delpiano, Delpiano E, Camanni M, Marco Camanni, Ezio Ghigo, Ghigo E, Riccarda Granata
Fertility and sterility · 2009 · vol. 94(3) , pp. 841–849 · doi:10.1016/j.fertnstert.2009.03.093 · PMID:19524226 · W2149480204
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The growth hormone-releasing hormone (GHRH) antagonist JV-1-36 was found to inhibit the proliferation and survival of human ectopic endometriotic stromal cells (ESCs) and the T HESC cell line.

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Abstract

ObjectiveTo 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.DesignProspective laboratory study.SettingUniversity hospital.Patient(s)22 women with endometriosis (aged 34.8+/-5.7 years) undergoing therapeutic laparoscopy.Intervention(s)Eutopic (n=10) and ectopic (n=22) endometrial tissues were collected from women who underwent therapeutic laparoscopic surgery for endometriosis (stage III/IV).Main outcome measure(s)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.Result(s)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.Conclusion(s)The GHRH antagonist JV-1-36 inhibits endometriotic cell proliferation and survival, suggesting that GHRH antagonist may represent promising tools for treatment of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Cell Proliferation Choristoma Endometriosis Growth Hormone-Releasing Hormone Stromal Cells Uterine Diseases Adult Cell Line, Transformed Cell Proliferation Cells, Cultured Cell Survival Cell Survival Choristoma Choristoma Choristoma Drug Evaluation, Preclinical Endometriosis Endometriosis Endometriosis Endometrium

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