title: Dopamine agonist inhibits vascular endothelial growth factor protein production and secretion in granulosa cells.
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).
  
  
  RESULTS
  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 Gi/Go, Gz and AKT/β-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.
authors.affiliation: Fundación IVI, C/ Catedrático Agustín Escardino, n°9, Paterna, Valencia, 46980, Spain. hortensia.ferrero@ivi.es.|Instituto Universitario IVI/ INCLIVA, Valencia, 46015, Spain. hortensia.ferrero@ivi.es.
authors.forename: Hortensia
authors.initials: H
authors.lastname: Ferrero
authors.affiliation: Fundación IVI, C/ Catedrático Agustín Escardino, n°9, Paterna, Valencia, 46980, Spain. carmen.m.garcia@uv.es.|Instituto Universitario IVI/ INCLIVA, Valencia, 46015, Spain. carmen.m.garcia@uv.es.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: García-Pascual
authors.affiliation: Fundación IVI, C/ Catedrático Agustín Escardino, n°9, Paterna, Valencia, 46980, Spain. n.pellicerdc@gmail.com.
authors.forename: Nuria
authors.initials: N
authors.lastname: Pellicer
authors.affiliation: Fundación IVI, C/ Catedrático Agustín Escardino, n°9, Paterna, Valencia, 46980, Spain. carlos.simon@ivi.es.|Instituto Universitario IVI/ INCLIVA, Valencia, 46015, Spain. carlos.simon@ivi.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
authors.affiliation: Fundación IVI, C/ Catedrático Agustín Escardino, n°9, Paterna, Valencia, 46980, Spain. apellicer@ivi.es.|Hospital Universitario i Politécnico La Fe, Valencia, 46026, Spain. apellicer@ivi.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellicer
authors.affiliation: Instituto Universitario IVI/ INCLIVA, Valencia, 46015, Spain. raulgomgal@gmail.com.
authors.forename: Raúl
authors.initials: R
authors.lastname: Gómez
mesh_terms: D000328:Adult; D000077465:Cabergoline; D018491:Dopamine Agonists / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C581293:DRD2 protein, human; D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077465:Cabergoline