INTERFERON-ALPHA DOWN-REGULATES EXPRESSION OF THE OXYTOCIN RECEPTOR IN CULTURED HUMAN MYOMETRIAL CELLS

Previous studies in the endometrium of ruminants showed that type I in terferon (IFN) prevents oxytocin receptor (OTR) formation. We studied the effect of IFN-alpha on human myometrial cells in culture expressin g a high density of biologically active OTR. We found that IFN-alpha i nduced a 35-50% decrease in OTR mRNA and protein and that this inhibit ion was time and dose dependent. Maximal inhibition of OTR mRNA was ob tained after 2-3 days, whereas ta-mercapto-beta,beta-cyclopentamethyle nepropionic e-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 inhibi tory concentration (IC50) = 1,100 U/ml. Mathematical analysis of multi ple homologous competition curves for [I-125]OTA indicated that IFN-al pha treatment (5.000 U/ml x 3 days) reduced just the binding capacity (B-max) without changing the binding affinity. Accordingly the same tr eatment with IFN-alpha did not affect the half-maximally effective con centration (EC(50)) for the oxytocin-induced increase in intracellular calcium but significantly decreased maximal responsiveness (E(max)) o f myometrial cells to OT stimulation. In conclusion, our data demonstr ate. for the first time, a negative regulation by IFN-alpha of the ste ady-state expression of OTR mRNA in cultured human myometrial cells ob tained from nonpregnant uteri. This inhibition was followed by a paral lel decrease in both the B-max for [I-125]OTA and E(max) for oxytocin, suggesting a decreased OTR protein availability.