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EndothelinA receptors in human uterine leiomyomas
M Breuiller-Fouché1, M C Vacher-Lavenu, T Fournier
1Institut National de la Santé et de la Recherche Médicale INSERM U.361, The Service de Gynécologie Obstétrique II à orientation gynécologique, Pavillon Baudelocque, Paris, France. u361@cochin.inserm.fr
Objective:
To determine if there are endothelin receptors on human uterine leiomyomas.
Methods:
Samples of leiomyomas from eight patients were analyzed for [iodine (I)-125]endothelin-1 binding. Several subtype-selective ligands were used to determine the endothelin receptor population.
Results:
Binding of [125I]endothelin-1 to uterine leiomyoma membranes was specific and saturable, with a mean +/- dissociation constant 85.5 +/- 8.4 pM. Competition binding studies showed that the order of potency was endothelin-1 > endothelin-3, which was consistent with the presence of the endothelinA receptor subtype. Binding of [125I]endothelin-1 was displaced by an endothelinA-selective antagonist, but not by sarafotoxin 6c, an endothelinB-selective agonist. An endothelins-selective ligand was not specifically bound to leiomyoma.
Conclusion:
These results indicate that only endothelinA receptors are present in human uterine leiomyomas. We speculate that endothelin-1 may act through these endothelinA receptors to influence the development or regulation of hypertrophy and proliferation of the human myometrium during pregnancy and in uterine disorders like leiomyomas.