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

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.

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


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).

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

University affiliated infertility center.

Premenopausal women and egg donors.

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.

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.

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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