Dopamine agonist administration causes a reduction in endometrial implants through modulation of angiogenesis in experimentally induced endometriosis

Edurne Novella-Maestre, Novella-Maestre E, Carmen Carda, Carmen Cardá, Carda C, Noguera I, Inmaculada Noguera, Ruiz-Saurí A, Amparo Ruiz‐Saurí, Amparo Ruiz-Saurí, Juan A. García-Velasco, Juan Antonio García-Velasco, Carlos Simón, António Pellicer, Antonio Pellicer
Human Reproduction · 2009 · vol. 24(5) , pp. 1025–1035 · doi:10.1093/humrep/den499 · PMID:19189995 · W2131145289
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Cabergoline treatment reduced endometriotic lesion size and cellular proliferation in mice by decreasing neoangiogenesis and VEGFR-2 phosphorylation.

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Abstract

BACKGROUND: Implantation of a retrogradely-shed endometrium during menstruation requires an adequate blood supply. The endometrium has angiogenic potential, and endometriotic lesions grow in areas with a rich vascularization, suggesting that angiogenesis is a prerequisite for endometriosis development. Targeting vascular endothelial growth factor (VEGF) leads to an inhibition of endometriosis. Dopamine and its agonists, such as cabergoline (Cb2), promote VEGF receptor-2 (VEGFR-2) endocytosis in endothelial cells, preventing VEGF-VEGFR-2 binding and reducing neoangiogenesis. The aim of this study was to evaluate the anti-angiogenic properties of Cb2 on growth of established endometriosis lesions and investigate the molecular mechanisms by which Cb2 exerts the anti-angiogenic effect. METHODS: Human endometrium fragments were implanted in female nude mice peritoneum, and mice were treated with vehicle, 0.05 or 0.1 mg/kg/day oral Cb2 for 14 days. After treatment, the implants were processed to assess proliferative activity, neoangiogenesis, VEGFR-2 phosphorylation and angiogenic gene expression. RESULTS: A significant decrease in the percentage of active endometriotic lesions (P < 0.05) and cellular proliferation index (P < 0.001) was found with Cb2 treatment. Neoangiogenesis was reduced by Cb2 treatment, as observed at gross morphological level and by significant changes in gene expression. The degree of VEGFR-2 phosphorylation was significantly lower in Cb2-treated animals than controls. CONCLUSIONS: Cb2 treatment in experimental endometriosis has an anti-angiogenic effect acting through VEGFR-2 activation. These findings support the testing of dopamine agonists as a novel therapeutic approach to peritoneal endometriosis in humans.

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Condition tags

endometriosis

MeSH descriptors

Dopamine Agonists Endometriosis Ergolines Neovascularization, Pathologic Animals Animals Cabergoline Cabergoline Cell Proliferation Cell Proliferation Cell Proliferation Disease Models, Animal Disease Models, Animal Dopamine Agonists Dopamine Agonists Endometriosis Endometriosis Endometriosis Ergolines Ergolines

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

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