The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis
| Autor: | Francisco Gaytan, Raúl Gómez, Hortensia Ferrero, Carlos Simón, Francisco Delgado-Rosas, Juan A. Garcia-Velasco, Antonio Pellicer |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Embryology
medicine.medical_specialty Cabergoline Proliferation index Angiogenesis Endometriosis Cell Count Pharmacology Dopamine agonist Claviceps Neovascularization Endometrium Mice chemistry.chemical_compound Endocrinology Internal medicine medicine Animals Humans Ergolines Cell Proliferation Uterine Diseases Neovascularization Pathologic Receptors Dopamine D2 business.industry Quinagolide Obstetrics and Gynecology Cell Biology medicine.disease Vascular Endothelial Growth Factor Receptor-2 Vascular endothelial growth factor Disease Models Animal Reproductive Medicine chemistry Dopamine Agonists Blood Vessels Female medicine.symptom business medicine.drug |
| Zdroj: | REPRODUCTION. 142:745-755 |
| ISSN: | 1741-7899 1470-1626 |
| DOI: | 10.1530/rep-11-0223 |
| Popis: | Implantation of a retrogradely shed endometrium during menstruation requires an adequate blood supply, which allows the growth of endometriotic lesions. This suggests that the development of endometriosis can be impaired by inhibiting angiogenesis. The growth of endometriotic foci is impaired by commercial oncological antiangiogenic drugs used to block vascular endothelial growth factor (VEGF) signaling. The dopamine agonist cabergoline (Cb2) inhibits the growth of established endometriosis lesions by exerting antiangiogenic effects through VEGFR2 inactivation. However, the use of ergot-derived Cb2 is associated with an increased incidence of cardiac valve regurgitation. To evaluate the potential usage of non-ergot-derived dopamine agonists for the treatment of human endometriosis, we compared the efficacy of quinagolide with that of Cb2 in preventing angiogenesis and vascularization in a heterologous mouse model of endometriosis. Nude mice whose peritoneum had been implanted with eutopic human endometrial fragments were treated with vehicle, 50 μg/kg per day oral Cb2, or 50 or 200 μg/kg per day quinagolide during a 14-day period. At the end of the treatment period, the implants were excised in order to assess lesion size, cell proliferation, degree of vascularization, and angiogenic gene expression. Neoangiogenesis was inhibited and the size of active endometriotic lesions, cellular proliferation index, and angiogenic gene expression were significantly reduced by both dopamine agonists when compared with the placebo. Given that Cb2 and quinagolide were equally effective in inhibiting angiogenesis and reducing lesion size, these experiments provide the rationale for pilot studies to explore the use of non-ergot-derived dopamine agonists for the treatment of endometriosis in humans. |
| Databáze: | OpenAIRE |
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