EndothelinA receptors in human uterine leiomyomas.
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.


CONCLUSIONS
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.
Breuiller-Fouché
M
M
Institut 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
Vacher-Lavenu
M C
MC
Fournier
T
T
Morice
P
P
Dubuisson
J B
JB
Ferré
F
F
D000328:Adult; D019332:Endothelin-1 / Q000378:metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000737:chemistry*; D008875:Middle Aged; D011869:Radioligand Assay; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000032:analysis*; D014594:Uterine Neoplasms / Q000737:chemistry*; D014599:Uterus / Q000737:chemistry
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin