Interferon-[alpha] down-regulates the expression of oxytocin
receptor in cultured human myometrial cells.
Maggi, Mario, Alessandro Peri, Elisabetta Baldi, Rosa Mancina, Simone
Granchi, Guido Fantoni, Giovanna Finetti, Gianni Forti, Claudia
Casini Raggi, and Mario Serio.
Department of Clinical Physiopathology, Andrology and Endocrinology
Unit, University of Florence, 50139 Florence, Italy
APStracts 3:0167E, 1996.
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, while
[125I]OTA binding reached a nadir after 3-4 days, with an IC50=1100
U/ml. Mathematical analysis of multiple homologous competition curves
for [125I]OTA indicated that IFN-[alpha] treatment (5000 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 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 OT, suggesting a decreased OTR protein
availability.
Received 16 January 1996; accepted in final form 25 June 1996.
APS Manuscript Number E25-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996