The Journal of clinical endocrinology and metabolism · 2011
Evidences for the existence of a low dopaminergic tone in polycystic ovarian syndrome: implications for OHSS development and treatment.
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Gómez Raúl, Ferrero Hortensia, Delgado-Rosas Francisco, Gaytan Maria, Morales Concepción, Zimmermann Ralf C, Simón Carlos, Gaytan Francisco, Pellicer Antonio
Аннотация
CONTEXT: 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.
DESIGN: 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.
SETTING: The study was conducted at a private research center.
PATIENTS OR OTHER PARTICIPANTS: PCOS and nonpolycystic ovarian patients and oocyte patients participated in the study.
INTERVENTION(S): 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.
MAIN OUTCOME MEASURE(S): 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.
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.
DESIGN: 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.
SETTING: The study was conducted at a private research center.
PATIENTS OR OTHER PARTICIPANTS: PCOS and nonpolycystic ovarian patients and oocyte patients participated in the study.
INTERVENTION(S): 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.
MAIN OUTCOME MEASURE(S): 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.
Предметные рубрики MeSH
AdultCabergolineCells, CulturedDopamineDopamine AgonistsErgolinesFemaleGranulosa CellsHumansLuteal CellsNeovascularization, PhysiologicOocytesOvarian Hyperstimulation SyndromePolycystic Ovary SyndromeReceptors, Dopamine D2Risk FactorsSignal TransductionTissue BanksVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Young Adult