Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2015

Open Access 01-12-2015 | Short communication

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

Authors: Hortensia Ferrero, Carmen M. García-Pascual, Nuria Pellicer, Carlos Simón, Antonio Pellicer, Raúl Gómez

Published in: Reproductive Biology and Endocrinology | Issue 1/2015

Login to get access

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.
Literature
1.
Kaiser UB. The pathogenesis of the ovarian hyperstimulation syndrome. N Engl J Med. 2003;349:729–32.CrossRefPubMed
2.
Bates DO, Curry FE. Vascular endothelial growth factor increases hydraulic conductivity of isolated perfused microvessels. Am J Physiol. 1996;271:H2520–8.PubMed
3.
Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun. 1989;161:851–8.CrossRefPubMed
4.
Neulen J, Yan Z, Raczek S, Weindel K, Keck C, Weich HA, et al. Human chorionic gonadotropin-dependent expression of vascular endothelial growth factor/vascular permeability factor in human granulosa cells: importance in ovarian hyperstimulation syndrome. J Clin Endocrinol Metab. 1995;80:1967–71.PubMed
5.
Wang TH, Horng SG, Chang CL, Wu HM, Tsai YJ, Wang HS, et al. Human chorionic gonadotropin-induced ovarian hyperstimulation syndrome is associated with up regulation of vascular endothelial growth factor. J Clin Endocrinol Metab. 2002;87:3300–8.CrossRefPubMed
6.
Haas J, Ophir L, Barzilay E, Yerushalmi GM, Yung Y, Kedem A, et al. GnRH agonist vs. hCG for triggering of ovulation differential effects on gene expression in human granulosa cells. PLoS One. 2014;9, e90359.PubMedCentralCrossRefPubMed
7.
Kitajima Y, Endo T, Manase K, Nishikawa A, Shibuya M, Kudo R. Gonadotropin-releasing hormone agonist administration reduced vascular endothelial growth factor (VEGF), VEGF receptors, and vascular permeability of the ovaries of hyperstimulated rats. Fertil Steril. 2004;81 Suppl 1:842–9.CrossRefPubMed
8.
Youssef MA, Van der Veen F, Al-Inany HG, Mochtar MH, Griesinger G, Nagi Mohesen M, et al. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology. Cochrane Database Syst Rev. 2014;10, CD008046.PubMed
9.
Basu S, Nagy JA, Pal S, Vasile E, Eckelhoefer IA, Bliss Vs et al. The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor. Nat Med. 2001;7:569–74.CrossRefPubMed
10.
Cristina C, Díaz-Torga G, Baldi A, Góngora A, Rubinstein M, Low MJ, et al. Increased pituitary vascular endothelial growth factor-a in dopaminergic D2 receptor knockout female mice. Endocrinology. 2005;146:2952–62.CrossRefPubMed
11.
Sinha S, Vohra PK, Bhattacharya R, Dutta S, Sinha S, Mukhopadhyay D. Dopamine regulates phosphorylation of VEGF receptor 2 by engaging Src-homology-2-domain-containing protein tyrosine phosphatase 2. J Cell Sci. 2009;122:3385–92.PubMedCentralCrossRefPubMed
12.
Bodis J, Bognar Z, Hartmann G, Torok A, Csaba IF. Measurement of noradrenaline, dopamine and serotonin contents in follicular fluid of human graafian follicles after superovulation treatment. Gynecol Obstet Invest. 1992;33:165–7.CrossRefPubMed
13.
Lara HE, Porcile A, Espinoza J, Romero C, Luza SM, Fuhrer J, et al. Release of norepinephrine from human ovary: coupling to steroidogenic response. Endocrine. 2001;15:187–92.CrossRefPubMed
14.
15.
Gómez R, Gonzalez-Izquierdo M, Zimmermann RC, Novella-Maestre E, Alonso-Muriel I, Sanchez-Criado J, et al. Low dose dopamine agonist administration blocks VEGF mediated vascular permeability without altering VEGFR-2 dependent luteal angiogenesis in a rat ovarian hyperstimulation model. Endocrinology. 2006;147:5400–11.CrossRefPubMed
16.
Álvarez C, Martí-Bonmatí L, Novella-Maestre E, Sanz R, Gómez R, Fernández-Sánchez M, et al. Dopamine agonist cabergoline reduces hemoconcentration and ascites in hyperstimulated women undergoing assisted reproduction. J Clin Endocrinol Metab. 2007;92:2931–7.CrossRefPubMed
17.
Ferrero H, García-Pascual CM, Gómez R, Delgado-Rosas F, Cauli O, Simón C, et al. Dopamine receptor 2 activation inhibits ovarían vascular endothelial growth factor secretion in vitro: implications for treatment of ovarían hyperstimulation syndrome with dopamine receptor 2 agonists. Fertil Steril. 2014;101:1411–8.CrossRefPubMed
18.
Ferrero H, García-Pascual CM, Gaytán M, Morales C, Simón C, Gaytán F, et al. Dopamine receptor 2 activation inhibits ovarian vascular endothelial growth factor secretion in an ovarian hyperstimulation sysndrome (OHSS) animal model: implications for treatment of OHSS with dopamine receptor 2 agonists. Fertil Steril. 2014;102:1468–76.CrossRefPubMed
19.
Youssef MA, Van Wely M, Hassan MA, Al-Inany HG, Mochtar M, Khattab S, et al. Can dopamine agonists reduce the incidence and severity of OHSS in IVF/ICSI treatment cycles? A systematic review and meta-analysis. Hum Reprod Update. 2010;16:459–66.CrossRefPubMed
20.
Gonzales-Iglesias AE, Murano T, Li S, Tomic M, Stojilkowic SS. Dopamine inhibits basal prolactin release in pituitary lactotrophs through pertussis toxin-sensitive and insensitive signaling pathways. Endocrinology. 2008;149:1470–9.CrossRef
21.
Ferrero H, Delgado-Rosas F, Garcia-Pascual CM, Monterde M, Zimmermann RC, Simón C, et al. Efficiency and purity provided by the existing methods for the isolation of luteinized granulose cells: a comparative study. Hum Reprod. 2012;27:1781–9.CrossRefPubMed
22.
Matkowskyj KA, Schonfeld D, Benya RV. Quantitative immunohistochemistry by measuring cumulative signal strength using commercially available software photoshop and matlab. J Histochem Cytochem. 2000;48:303–12.CrossRefPubMed
23.
Sarkar C, Chakroborty D, Basu Mitra R, Banerjee S, Dasgupta PS, Basu S. Dopamine in vivo inhibits VEGF-induced phosphorylation of VEGFR-2, MAPK, and focal adhesion kinase in endothelial cells. Am J Physiol Heart Circ Physiol. 2004;287:H1554–60.
24.
Chen SU, Chou CH, Lin CW, Lee H, Wu JC, Lu HF, et al. Signal mechanisms of vascular endothelial growth factor and interleukin-8 in ovarian hyperstimulation syndrome: dopamine targets their common pathways. Hum Reprod. 2010;25:757–67.
25.
Stocco C, Telleria C, Gibori G. The molecular control of corpus luteum formation, function, and regression. Endocr Rev. 2007;28:117–49.CrossRefPubMed
26.
Moreno-Smith M, Lee SJ, Lu C, Nagaraja AS, He G, Rupaimoole R, et al. Biologic effects of dopamine on tumor vasculature in ovarian carcinoma. Neoplasia. 2013;15:502–10.PubMedCentralCrossRefPubMed
Metadata
Title
Dopamine agonist inhibits vascular endothelial growth factor protein production and secretion in granulosa cells
Authors
Hortensia Ferrero
Carmen M. García-Pascual
Nuria Pellicer
Carlos Simón
Antonio Pellicer
Raúl Gómez
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2015
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-015-0102-4

Other articles of this Issue 1/2015

Reproductive Biology and Endocrinology 1/2015 Go to the issue

Research

Age-related trends in anti-Mullerian hormone serum level in women with unilateral and bilateral ovarian endometriomas prior to surgery

Research

Gene expression analysis of pig cumulus-oocyte complexes stimulated in vitro with follicle stimulating hormone or epidermal growth factor-like peptides

Research

In the pubertal rat, the regulation of ovarian function involves the synergic participation of the sensory and sympathetic innervations that arrive at the gonad

Editorial

Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases

Editorial

Infertility etiologies are genetically and clinically linked with other diseases in single meta-diseases

Research

Influence of ejaculation frequency on seminal parameters