Interferon-alpha downregulates expression of the oxytocin receptor in cultured human myometrial cells

Previous studies in the endometrium of ruminants showed that type I interferon (IFN) prevents oxytocin receptor (OTR) formation. We studied the effect of IFN-alpha on human myometrial cells in culture expressing a high density of biologically active OTR. We found that IFN-alpha induced a 35-50% decrease in OTR mRNA and protein and that this inhibition was time and dose dependent. Maximal inhibition of OTR mRNA was obtained after 2-3 days, whereas 1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid,2-O-Me-Tyr,Thr(4),Orn(8),Tyr(9)-amide)-[I-125]vasotocin ([I-125]OTA) binding reached a nadir after 3-4 days, with half-maximal inhibitory concentration (IC50) = 1,100 U/ml. Mathematical analysis of multiple homologous competition curves for [I-125]OTA indicated that IFN-alpha treatment (5.000 U/ml x 3 days) reduced just the binding capacity (B-max) without changing the binding affinity. Accordingly the same treatment with IFN-alpha did not affect the half-maximally effective concentration (EC(50)) for the oxytocin-induced increase in intracellular calcium but significantly decreased maximal responsiveness (E(max)) of myometrial cells to OT stimulation. In conclusion, our data demonstrate. for the first time, a negative regulation by IFN-alpha of the steady-state expression of OTR mRNA in cultured human myometrial cells obtained from nonpregnant uteri. This inhibition was followed by a parallel decrease in both the B-max for [I-125]OTA and E(max) for oxytocin, suggesting a decreased OTR protein availability.