title: Dopamine receptor 2 activation inhibits ovarian vascular endothelial growth factor secretion in vitro: implications for treatment of ovarian hyperstimulation syndrome with dopamine receptor 2 agonists.
abstract: OBJECTIVE
  To ascertain whether vascular endothelial growth factor (VEGF) secretion by luteinized granulosa cells (GCs) is modulated by the dopaminergic system in a dose-dependent fashion and how this is related to the differential efficacy of dopamine receptor 2 (D2)-agonists (D2-ag) in preventing ovarian hyperstimulation syndrome (OHSS).
  
  
  METHODS
  The relationship between the dopaminergic system and VEGF secretion in luteinized GCs was evaluated. Archived human ovaries were immunostained to characterize D2 expression.
  
  
  METHODS
  University affiliated infertility center.
  
  
  METHODS
  Premenopausal women and egg donors.
  
  
  METHODS
  Luteinized GCs were cultured with the D2-ag cabergoline. Human ovarian sections were immunostained for D2.
  
  
  METHODS
  The VEGF was measured by ELISA and D2 expression was evaluated by In-Cell ELISA. The D2 expression throughout the luteal phase was characterized by immunohistochemistry.
  
  
  RESULTS
  The VEGF secretion was decreased by the D2-ag in a dose-dependent fashion. The efficiency of this process was correlated with the amount of D2 expressed by luteinized GCs. A decrease in D2 expression in ovarian sections was observed during the late luteal phase.
  
  
  CONCLUSIONS
  The efficacy of D2-ags in preventing OHSS might rely on their capacity to inhibit VEGF secretion by luteinized GCs. Because this capacity is dose-dependent, increasing the intraovarian concentration of D2-ags should be explored as a means of increasing the efficacy of these drugs in preventing OHSS.
authors.affiliation: Fundación IVI, Instituto Universitario IVI/INCLIVA Biomedical Research Institute, Valencia, Spain.
authors.forename: Hortensia
authors.initials: H
authors.lastname: Ferrero
authors.affiliation: Fundación IVI, Instituto Universitario IVI/INCLIVA Biomedical Research Institute, Valencia, Spain.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: García-Pascual
authors.affiliation: Fundación IVI, Instituto Universitario IVI/INCLIVA Biomedical Research Institute, Valencia, Spain. Electronic address: raul.gomez@ivi.es.
authors.forename: Raúl
authors.initials: R
authors.lastname: Gómez
authors.affiliation: IVI-Madrid, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Delgado-Rosas
authors.affiliation: Department of Nursing, University of Valencia, Valencia, Spain.
authors.forename: Omar
authors.initials: O
authors.lastname: Cauli
authors.affiliation: Fundación IVI, Instituto Universitario IVI/INCLIVA Biomedical Research Institute, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, University of Córdoba, Cordoba, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gaytán
authors.affiliation: Fundación IVI, Instituto Universitario IVI/INCLIVA Biomedical Research Institute, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D018491:Dopamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D016471:Ovarian Hyperstimulation Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010865:Pilot Projects; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: C581293:DRD2 protein, human; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: OHSS; VEGF; dopamine receptor 2; dopamine receptor 2 agonist; granulosa cells