INDUCTION OF OXYTOCIN RECEPTOR GENE-EXPRESSION IN RABBIT AMNION CELLS

Oxytocin (OT)-stimulated PGE(2) release by rabbit amnion is enhanced b y the up-regulation of oxytocin receptors (OTR), which increase about 200-fold at the end of pregnancy. As recent studies have shown that PG s are essential for parturition, the rise in amnion OTR and associated PGE(2) synthesis are probably essential for labor initiation. The pre sent work was directed toward understanding the mechanisms of OTR up-r egulation. Levels of agents that stimulate adenylyl cyclase activity a nd cortisol are increased in amniotic fluid at the end of pregnancy. A ddition of either forskolin or cortisol to cultured amnion cells cause d an increase in OTR ligand-binding sites and steady state OTR messeng er RNA (mRNA) levels. Forskolin treatment elevated OTR mRNA levels rap idly, but transiently, whereas cortisol's effects were slower and sust ained. Actinomycin or cycloheximide, added 3 h after forskolin, led to a sustained elevation in OTR mRNA levels, suggesting that forskolin i ncreases the activities of OTR mRNA-destabilizing factors along with i ncreasing OTR mRNA concentration. Cortisol did not appear to affect OT R mRNA stability. Measurement of OTR mRNA transcription rates showed t hat forskolin's effects were maximal within 1 h of treatment. In contr ast, cortisol-induced transcription was not apparent until 8 h. The ef fects of forskolin and cortisol on OTR gene transcription were synergi stic. Thus, the increase in OTR mRNA levels occurring after either for skolin or cortisol treatments is the result of induction of OTR gene e xpression, but the effects of the two agents appear to occur at separa te sites.