Expression and regulation of prostaglandin receptors and cytochrome P450c17 hydroxylase in the late gestation ovine placenta

Previous studies in sheep reported that fetal cortisol produced in late gestation causes increased placental PGHS-2 expression and PGE 2 synthesis. It has been suggested that PGE2, acting through prostaglandin receptors, upregulates placental P450c17 resulting in altered placental steroid synthesis at term. Using a glucocorticoid-induced ovine model of preterm labour, we demonstrated significant increases in placental PGHS-2 protein expression and fetal plasma PGE2 which were associated with P450c17 mRNA upregulation after intrafetal cortisol infusion. Co-infusion with meloxicam increased P450c17 expression despite blocking PGE2 synthesis. We also localized EP1, EP3, and FP receptors to uninucleate cells of the fetal trophoblast. However, increased exogenous and endogenous (by periconceptional undernutrition) cortisol had no effect on altering prostaglandin receptor expression. Therefore, we suggest that increased PGE2 output in late gestation may not be the major pathway in regulating P450c17 and that cortisol and/or other glucocorticoid-stimulated intermediates could play a role in regulation of placental P450c17.