Dopamine agonist inhibits vascular endothelial growth factor protein production and secretion in granulosa cells

Autores de IIS La Fe

• Hortensia Ferrero Chafer

  Autor

• Carmen Maria Garcia Pascual

  Autor

• Carlos Simon Valles

  Autor

• Antonio Pellicer Martínez

  Autor

Participantes ajenos a IIS La Fe

• Pellicer N
• Gómez R

Grupos

• Medicina Reproductiva

  

  Investigador Principal

  José Morales Roselló

Abstract

Background: Dopamine receptor 2 agonists (D2-ags) inhibit vascular endothelial growth factor (VEGF) secretion in luteinized granulosa cells (LGCs) both in vitro and in vivo. However, the mechanism of D2 regulation of the VEGF/ VEGF Receptor 2 (VEGFR-2) pathway remains to be elucidated. We sought to determine the effects of D2 signaling on VEGF transcription and translation in LGCs, with the expectation of identifying potential D2-ag-based therapies for ovarian hyperstimulation syndrome (OHSS). Findings: LGCs from egg donors were cultured with chorionic gonadotropin (hCG) in the presence of Actinomycin-D (ActD) or Brefeldin-A (BFA) to evaluate the effects of a D2-ag, cabergoline (Cb2), on VEGF secretion. The contribution of the conventional G(i)/G(o), G(z) and AKT/beta-Arrestin pathways in the VEGF regulation was assessed by adding pertussis toxin (PTX), phorbol 12-myristate 13-acetate (PMA), or wortmannin (WT). While Cb2 inhibited VEGF secretion by interfering with VEGF peptide translation and secretion, inhibition of conventional D2 transduction pathways did not reverse Cb2-mediated inhibition of VEGF secretion. Conclusions: The effects of D2-ag on VEGF translation and secretion are mediated by D2 signaling pathways that have yet to be described. We found that D2-ag inhibits VEGF secretion at the post-transcriptional level, suggesting that D2-ag treatment should be combined with therapies that inhibit VEGF transcription, such as the employment of LH or GnRH for triggering ovulation, to improve the efficacy of OHSS prevention.

Keywords

• OHSS; VEGF; Granulosa cells; Dopamine receptor 2; Dopamine receptor-2 agonist