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

Capsule:
Dopamine receptor 2 agonists inhibit VEGF secretion in a dose-dependent fashion, which is directly dependent on the amount of D2 expressed by luteinized granulosa cells.

Authors:
Hortensia Ferrero, Ph.D., Carmen M. García-Pascual, Ph.D., Raúl Gómez, Ph.D., Francisco Delgado-Rosas, Ph.D., Omar Cauli, Ph.D., Carlos Simón, M.D., Francisco Gaytán, M.D., Antonio Pellicer, M.D.

Volume 101, Issue 5, Pages 1411–1418.e2

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).

Design:
The relationship between the dopaminergic system and VEGF secretion in luteinized GCs was evaluated. Archived human ovaries were immunostained to characterize D2 expression.

Setting:
University affiliated infertility center.

Patient(s):
Premenopausal women and egg donors.

Intervention(s):
Luteinized GCs were cultured with the D2-ag cabergoline. Human ovarian sections were immunostained for D2.

Main Outcome Measure(s):
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.

Result(s):
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.

Conclusion(s):
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.

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