AJP - Endocrinology and Metabolism, Vol 271, Issue 5 E840-E846, Copyright © 1996 by American Physiological Society
Interferon-alpha downregulates expression of the oxytocin receptor in cultured human myometrial cells
M. Maggi, A. Peri, E. Baldi, R. Mancina, S. Granchi, G. Fantoni, G. Finetti, G. Forti, C. C. Raggi and M. Serio
Department of Clinical Physiopathology, University of Florence, Italy.
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-cyclopentamethyl-enepropionic
acid,2-O-Me-Tyr,Thr4,Orn8,Tyr9-amide)-[125I]vasotocin ([125I]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 [125I]OTA indicated that IFN-alpha treatment (5,000
U/ml x 3 days) reduced just the binding capacity (Bmax) without changing
the binding affinity. Accordingly, the same treatment with IFN-alpha did
not affect the half-maximally effective concentration (EC50) for the
oxytocin-induced increase in intracellular calcium but significantly
decreased maximal responsiveness (Emax) 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 Bmax for
[125I]OTA and Emax for oxytocin, suggesting a decreased OTR protein
availability.
