title: The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis.
abstract: 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.
authors.affiliation: Fundacion IVI-Instituto Universitario IVI, INCLIVA, Universidad de Valencia, C/Guadassuar 1 Bajo, 46015 Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Delgado-Rosas
authors.forename: Raúl
authors.initials: R
authors.lastname: Gómez
authors.forename: Hortensia
authors.initials: H
authors.lastname: Ferrero
authors.forename: Francisco
authors.initials: F
authors.lastname: Gaytan
authors.forename: Juan
authors.initials: J
authors.lastname: Garcia-Velasco
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D000077465:Cabergoline; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002967:Claviceps / Q000737:chemistry; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000302:isolation & purification / Q000494:pharmacology*; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004873:Ergolines / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D014591:Uterine Diseases / Q000378:metabolism / Q000473:pathology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077465:Cabergoline