A. Hinko et Ms. Soloff, UP-REGULATION OF OXYTOCIN RECEPTORS IN RABBIT AMNION BY GLUCOCORTICOIDS - POTENTIATION BY CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE, Endocrinology, 133(4), 1993, pp. 1511-1519
Oxytocin (OT) receptors (OTR) in rabbit amnion increase more than 200-
fold at the end of gestation. In the present report, we studied the ba
sis of this up-regulation. Incubation of amnion cells with cortisol (2
0 nm) for 24 h increased the amount of I-125-labeled OT antagonist bou
nd by 16- to 18-fold. The effects of cortisol were dose and steroid de
pendent. Administration of glucocorticoid to pregnant does also increa
sed the concentration of OTRs in amnion. The effects of cortisol in vi
tro were potentiated by the addition of forskolin (50 muM), so that OT
R number increased by as much as 182 times. The effects of cortisol an
d forskolin, either separately or in combination, were inhibited by ac
tivation of protein kinase-C or coincubation with transforming growth
factor-alpha (10 nm). Cyclosporin-A (5 muM) selectively inhibited cort
isol-induced rises in the OTR concentration. The addition of cortisol
to amnion cells increased OT-stimulated prostaglandin E2 (PGE2) releas
e almost 100-fold; the combination of forskolin and cortisol increased
the PGE2 response to OT about 5600 times. Judging from the greater ef
fects on PGE2 release, these results suggest that forskolin and cortis
ol up-regulate the signal response mechanism to OT as well as the OTR
concentration. The findings show that changes occurring in the amnion
in vivo can be mimicked in vitro, and they elucidate the mechanism of
up-regulation of OTR concentrations.