Fertility and Sterility
Volume 94, Issue 3 , Pages 841-849, August 2010

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

  • Marta Annunziata, Ph.D.

      Affiliations

    • Laboratory of Molecular and Cellular Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy
    • Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
    • ,
  • Cristina Grande

      Affiliations

    • Laboratory of Molecular and Cellular Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy
    • Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
    • ,
  • Francesca Scarlatti, Ph.D.

      Affiliations

    • Laboratory of Molecular and Cellular Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy
    • Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
    • ,
  • Francesco Deltetto, M.D.

      Affiliations

    • Ginteam, Unit of Minimally Invasive Gynecology, Turin, Italy
    • ,
  • Elena Delpiano, M.D.

      Affiliations

    • Ginteam, Unit of Minimally Invasive Gynecology, Turin, Italy
    • ,
  • Marco Camanni, M.D.

      Affiliations

    • Ginteam, Unit of Minimally Invasive Gynecology, Turin, Italy
    • ,
  • Ezio Ghigo, M.D.

      Affiliations

    • Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
    • ,
  • Riccarda Granata, Ph.D.

      Affiliations

    • Laboratory of Molecular and Cellular Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy
    • Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
    • Corresponding Author InformationReprint requests: Riccarda Granata, Ph.D., Laboratory of Molecular and Cellular Endocrinology, Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy (FAX: (+39) 011 664 74 21).

Received 8 January 2009; received in revised form 24 March 2009; accepted 26 March 2009. published online 12 June 2009.

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.

Design

Prospective laboratory study.

Setting

University 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.

Key Words: Endometriosis, growth hormone-releasing hormone (GHRH), GHRH receptor (GHRH-R), GHRH antagonists

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 M.A. has nothing to disclose. C.G. has nothing to disclose. F.S. has nothing to disclose. F.D. has nothing to disclose. E.D. has nothing to disclose. M.C. has nothing to disclose. E.G. has nothing to disclose. R.G. has nothing to disclose.

 Supported by grants from the Regione Piemonte (2006 and 2008 to E.G.; 2008 to R.G.) and the University of Turin (2006 to E.G; 2007 and 2008 to E.G. and R.G.) and by Ginteam (Turin, Italy).

PII: S0015-0282(09)00763-8

doi:10.1016/j.fertnstert.2009.03.093

Fertility and Sterility
Volume 94, Issue 3 , Pages 841-849, August 2010

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