UP-REGULATION OF OXYTOCIN RECEPTORS IN RABBIT AMNION BY GLUCOCORTICOIDS - POTENTIATION BY CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE

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.