title: Evidences for the existence of a low dopaminergic tone in polycystic ovarian syndrome: implications for OHSS development and treatment.
abstract: BACKGROUND
  The dopamine/dopamine receptor 2 (D2/Drd2) pathway modulates vascular endothelial growth factor (VEGF)-dependent vascular permeability and angiogenesis in the ovary. Deregulation of the VEGF/VEGF receptor (VEGFR)-2 pathway leading to increased risk of ovarian hyperstimulation syndrome has been described in the ovary of patients suffering from polycystic ovarian syndrome (PCOS).
  
  
  OBJECTIVE
  The objective of the study was to ascertain whether deregulation of the VEGF/VEGFR-2 might a least be partially due to abnormalities of the D2/Drd2 pathway in PCOS women.
  
  
  METHODS
  Dated, archived ovaries from PCOs and control group patients as well as human chorionic gonadotropin-stimulated luteinized granulosa cells form PCOS and non-PCOS oocyte patients were used.
  
  
  METHODS
  The study was conducted at a private research center.
  
  
  METHODS
  PCOS and nonpolycystic ovarian patients and oocyte patients participated in the study.
  
  
  METHODS
  Human ovarian sections were stained against the Drd2 antibody. Human chorionic gonadotropin-stimulated luteinized granulosa cells (LGC) were cultured in the presence/absence and the Drd2 agonist cabergoline.
  
  
  METHODS
  Drd2 and vascularized stained area in the theca layer of antral (< 8 mm) and luteinized follicles was quantified. VEGF, D2, and its related metabolites were measured in the supernatant of cultured LGC by ELISA and HPLC, respectively. VEGFR-2 and Drd2 expressed by LGC was quantified through an In-Cell ELISA.
  
  
  RESULTS
  Decreased Drd2 expression and increased vascularization in the theca layer of antral and luteinized follicles of PCOS ovaries was observed. A lower dopamine production and reduced efficacy of cabergoline in inhibiting VEGF secretion was uncovered in LGC from PCOS.
  
  
  CONCLUSIONS
  Decreased dopaminergic tone as well as deregulated Drd2 signaling might explain higher VEGF and vascularization leading to increased ovarian hyperstimulation syndrome risk in PCOS.
authors.affiliation: Fundacion IVI, Institituto Universitario IVI/Fundación Investigación Clinico de Valencia (INCLIVA), 46015 Valencia, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Gómez
authors.forename: Hortensia
authors.initials: H
authors.lastname: Ferrero
authors.forename: Francisco
authors.initials: F
authors.lastname: Delgado-Rosas
authors.forename: Maria
authors.initials: M
authors.lastname: Gaytan
authors.forename: Concepción
authors.initials: C
authors.lastname: Morales
authors.forename: Ralf C
authors.initials: RC
authors.lastname: Zimmermann
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
authors.forename: Francisco
authors.initials: F
authors.lastname: Gaytan
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D000328:Adult; D000077465:Cabergoline; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008184:Luteal Cells / Q000166:cytology / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D016471:Ovarian Hyperstimulation Syndrome / Q000453:epidemiology / Q000378:metabolism* / Q000628:therapy; D011085:Polycystic Ovary Syndrome / Q000453:epidemiology / Q000378:metabolism* / Q000628:therapy; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014015:Tissue Banks; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077465:Cabergoline; D004298:Dopamine