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Study · In vitro (cells) · mouse · 2019

6 results

GnRH Antagonists Produce Differential Modulation of the Signaling Pathways Mediated by GnRH Receptors.

Sperduti S, Limoncella S, Lazzaretti C, Paradiso E, Riccetti L, Turchi S, Ferrigno I, Bertacchini J, Palumbo C, Potì F, Longobardi S, Millar RP, Simoni M, Newton CL, Casarini L

International journal of molecular sciences7 Nov 2019Cited by 11 (Europe PMC)

PMID31703269 (opens in a new tab)PMCIDPMC6888270 (opens in a new tab)DOI10.3390/ijms20225548 (opens in a new tab)PepBankPUB-31703269
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Summary

Commercial gonadotropin-releasing hormone (GnRH) antagonists differ by 1-2 amino acids and are used to inhibit gonadotropin production during assisted reproduction technologies (ART). In this study, potencies of three GnRH antagonists, Cetrorelix, Ganirelix and Teverelix, in inhibiting GnRH-mediated intracellular signaling, were compared in vitro. GnRH receptor (GnRHR)-transfected HEK293 and neuroblastoma-derived SH-SY5Y cell lines, as well as mouse pituitary LβT2 cells endogenously expressing the murine GnRHR, were treated with GnRH in the presence or absence of the antagonist. We evaluated intracellular calcium (Ca2+) and cAMP increases, cAMP-responsive element binding-protein (CREB) and extracellular-regulated kinase 1 and 2 (ERK1/2) phosphorylation, β-catenin activation and mouse luteinizing-hormone β-encoding gene (Lhb) transcription by bioluminescence resonance energy transfer (BRET), Western blotting, immunostaining and real-time PCR as appropriate. The kinetics of GnRH-induced Ca2+ rapid increase revealed dose-response accumulation with potency (EC50) of 23 nM in transfected HEK293 cells, transfected SH-SY5Y and LβT2 cells. Cetrorelix inhibited the 3 × EC50 GnRH-activated calcium signaling at concentrations of 1 nM-1 µM, demonstrating higher potency than Ganirelix and Teverelix, whose inhibitory doses fell within the 100 nM-1 µM range in both transfected HEK293 and SH-SY5Y cells in vitro. In transfected SH-SY5Y, Cetrorelix was also significantly more potent than other antagonists in reducing GnRH-mediated cAMP accumulation. All antagonists inhibited pERK1/2 and pCREB activation at similar doses, in LβT2 and transfected HEK293 cells treated with 100 nM GnRH. Although immunostainings suggested that Teverelix could be less effective than Cetrorelix and Ganirelix in inhibiting 1 µM GnRH-induced β-catenin activation, Lhb gene expression increase occurring upon LβT2 cell treatment by 1 µM GnRH was similarly inhibited by all antagonists. To conclude, this study has demonstrated Cetrorelix-, Ganirelix- and Teverelix-specific biased effects at the intracellular level, not affecting the efficacy of antagonists in inhibiting Lhb gene transcription.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Mechanism

    In GnRHR-transfected human cell lines, ganirelix inhibited GnRH-activated calcium signaling with lower potency than cetrorelix.

    In plain wordsIn cells, ganirelix inhibited GnRH-activated calcium signaling with lower potency than cetrorelix.

    Peptide
    Ganirelix
    Outcome
    DecreaseCalcium-signaling inhibitory potency
    Study

    humann: not reported in source

    GnRHR-transfected HEK293 and SH-SY5Y cells
    Comparator
    Cetrorelix
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    100 nM-1 µMAs given in this study (human).

    Measurements

    Inhibitory concentration
    100 to 1000 nM
    ganirelix

    Source sentences

    Summary
    Cetrorelix inhibited the 3 × EC50 GnRH-activated calcium signaling at concentrations of 1 nM-1 µM, demonstrating higher potency than Ganirelix and Teverelix, whose inhibitory doses fell within the 100 nM-1 µM range in both transfected HEK293 and SH-SY5Y cells in vitro.
    2 context sentences
    Summary · context
    In this study, potencies of three GnRH antagonists, Cetrorelix, Ganirelix and Teverelix, in inhibiting GnRH-mediated intracellular signaling, were compared in vitro.
    Summary · context
    GnRH receptor (GnRHR)-transfected HEK293 and neuroblastoma-derived SH-SY5Y cell lines, as well as mouse pituitary LβT2 cells endogenously expressing the murine GnRHR, were treated with GnRH in the presence or absence of the antagonist.
  2. 02LabIn vitro (cells)Mechanism

    In GnRHR-transfected SH-SY5Y cells, ganirelix reduced GnRH-mediated cAMP accumulation less potently than cetrorelix.

    In plain wordsIn cells, ganirelix reduced GnRH-mediated cAMP accumulation less potently than cetrorelix.

    Peptide
    Ganirelix
    Outcome
    DecreasecAMP-signaling inhibitory potency
    Study

    humann: not reported in source

    GnRHR-transfected SH-SY5Y cells
    Comparator
    Cetrorelix
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In transfected SH-SY5Y, Cetrorelix was also significantly more potent than other antagonists in reducing GnRH-mediated cAMP accumulation.
    2 context sentences
    Summary · context
    In this study, potencies of three GnRH antagonists, Cetrorelix, Ganirelix and Teverelix, in inhibiting GnRH-mediated intracellular signaling, were compared in vitro.
    Summary · context
    GnRH receptor (GnRHR)-transfected HEK293 and neuroblastoma-derived SH-SY5Y cell lines, as well as mouse pituitary LβT2 cells endogenously expressing the murine GnRHR, were treated with GnRH in the presence or absence of the antagonist.
  3. 03LabIn vitro (cells)Mechanism

    In LβT2 and GnRHR-transfected HEK293 cells, ganirelix inhibited GnRH-induced ERK1/2 phosphorylation at doses similar to other antagonists.

    In plain wordsIn cells, ganirelix inhibited GnRH-induced ERK1/2 phosphorylation at doses similar to other antagonists.

    Peptide
    Ganirelix
    Outcome
    DecreaseERK1/2 phosphorylation
    Study

    human and mousen: not reported in source

    Mouse LβT2 and GnRHR-transfected human HEK293 cells
    Comparator
    GnRH without antagonist
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    All antagonists inhibited pERK1/2 and pCREB activation at similar doses, in LβT2 and transfected HEK293 cells treated with 100 nM GnRH.
    2 context sentences
    Summary · context
    In this study, potencies of three GnRH antagonists, Cetrorelix, Ganirelix and Teverelix, in inhibiting GnRH-mediated intracellular signaling, were compared in vitro.
    Summary · context
    GnRH receptor (GnRHR)-transfected HEK293 and neuroblastoma-derived SH-SY5Y cell lines, as well as mouse pituitary LβT2 cells endogenously expressing the murine GnRHR, were treated with GnRH in the presence or absence of the antagonist.
  4. 04LabIn vitro (cells)Mechanism

    In LβT2 and GnRHR-transfected HEK293 cells, ganirelix inhibited GnRH-induced CREB phosphorylation at doses similar to other antagonists.

    In plain wordsIn cells, ganirelix inhibited GnRH-induced CREB phosphorylation at doses similar to other antagonists.

    Peptide
    Ganirelix
    Outcome
    DecreaseCREB phosphorylation
    Study

    human and mousen: not reported in source

    Mouse LβT2 and GnRHR-transfected human HEK293 cells
    Comparator
    GnRH without antagonist
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    All antagonists inhibited pERK1/2 and pCREB activation at similar doses, in LβT2 and transfected HEK293 cells treated with 100 nM GnRH.
    2 context sentences
    Summary · context
    In this study, potencies of three GnRH antagonists, Cetrorelix, Ganirelix and Teverelix, in inhibiting GnRH-mediated intracellular signaling, were compared in vitro.
    Summary · context
    GnRH receptor (GnRHR)-transfected HEK293 and neuroblastoma-derived SH-SY5Y cell lines, as well as mouse pituitary LβT2 cells endogenously expressing the murine GnRHR, were treated with GnRH in the presence or absence of the antagonist.
  5. 05LabIn vitro (cells)Mechanism

    In cell immunostaining experiments, ganirelix appeared more effective than teverelix at inhibiting GnRH-induced beta-catenin activation.

    In plain wordsIn cells, ganirelix appeared more effective than teverelix at inhibiting GnRH-induced beta-catenin activation.

    Peptide
    Ganirelix
    Outcome
    DecreaseBeta-catenin activation
    Study

    n: not reported in source

    Comparator
    Teverelix
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Although immunostainings suggested that Teverelix could be less effective than Cetrorelix and Ganirelix in inhibiting 1 µM GnRH-induced β-catenin activation
    2 context sentences
    Summary · context
    In this study, potencies of three GnRH antagonists, Cetrorelix, Ganirelix and Teverelix, in inhibiting GnRH-mediated intracellular signaling, were compared in vitro.
    Summary · context
    GnRH receptor (GnRHR)-transfected HEK293 and neuroblastoma-derived SH-SY5Y cell lines, as well as mouse pituitary LβT2 cells endogenously expressing the murine GnRHR, were treated with GnRH in the presence or absence of the antagonist.
  6. 06LabIn vitro (cells)Mechanism

    In mouse LβT2 cells, ganirelix inhibited the GnRH-induced increase in Lhb expression similarly to other antagonists.

    In plain wordsIn cells, ganirelix inhibited GnRH-induced Lhb expression similarly to other antagonists.

    Peptide
    Ganirelix
    Outcome
    DecreaseLhb gene transcription
    Study

    mousen: not reported in source

    LβT2 cells
    Comparator
    GnRH without antagonist
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Lhb gene expression increase occurring upon LβT2 cell treatment by 1 µM GnRH was similarly inhibited by all antagonists.
    2 context sentences
    Summary · context
    In this study, potencies of three GnRH antagonists, Cetrorelix, Ganirelix and Teverelix, in inhibiting GnRH-mediated intracellular signaling, were compared in vitro.
    Summary · context
    GnRH receptor (GnRHR)-transfected HEK293 and neuroblastoma-derived SH-SY5Y cell lines, as well as mouse pituitary LβT2 cells endogenously expressing the murine GnRHR, were treated with GnRH in the presence or absence of the antagonist.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 3Current

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 2

    27 Oct 2026, 16:35 UTC

    Study data updated · source update from Europe PMC

  3. Version 1

    27 Oct 2026, 16:35 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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