Dopamine agonist inhibits vascular endothelial growth factor protein production and secretion in granulosa cells.

Abstract

BACKGROUND:

Dopamine receptor 2 agonists (D2-ags) inhibit vascular endothelial growth factor (VEGF) secretion in luteinized granulosa cells (LGCs) both in vitro and in vivo. However, the mechanism of D2 regulation of the VEGF/VEGF Receptor 2 (VEGFR-2) pathway remains to be elucidated. We sought to determine the effects of D2 signaling on VEGF transcription and translation in LGCs, with the expectation of identifying potential D2-ag-based therapies for ovarian hyperstimulation syndrome (OHSS).

FINDINGS:

LGCs from egg donors were cultured with chorionic gonadotropin (hCG) in the presence of Actinomycin-D (ActD) or Brefeldin-A (BFA) to evaluate the effects of a D2-ag, cabergoline (Cb2), on VEGF secretion. The contribution of the conventional Gi/Go, Gz and AKT/β-Arrestin pathways in the VEGF regulation was assessed by adding pertussis toxin (PTX), phorbol 12-myristate 13-acetate (PMA), or wortmannin (WT). While Cb2 inhibited VEGF secretion by interfering with VEGF peptide translation and secretion, inhibition of conventional D2 transduction pathways did not reverse Cb2-mediated inhibition of VEGF secretion.

CONCLUSIONS:

The effects of D2-ag on VEGF translation and secretion are mediated by D2 signaling pathways that have yet to be described. We found that D2-ag inhibits VEGF secretion at the post-transcriptional level, suggesting that D2-ag treatment should be combined with therapies that inhibit VEGF transcription, such as the employment of LH or GnRH for triggering ovulation, to improve the efficacy of OHSS prevention.

• Authors: Hortensia Ferrero, Carmen M García-Pascual, Nuria Pellicer, Carlos Simón, Antonio Pellicer, Raúl Gómez
• Journal: Reproductive biology and endocrinology : RB&E (Reprod Biol Endocrinol) Vol. 13 Pg. 104 (Sep 17 2015) ISSN: 1477-7827 [Electronic] England
• PMID: 26377185 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DRD2 protein, human
• Dopamine Agonists
• Ergolines
• Receptors, Dopamine D2
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Cabergoline

Topics

• Adult
• Cabergoline
• Dopamine Agonists (pharmacology)
• Ergolines (pharmacology)
• Female
• Granulosa Cells (drug effects, metabolism)
• Humans
• Receptors, Dopamine D2 (agonists, metabolism)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, biosynthesis, metabolism)