Throughout gestation, the chorion laeve controls the levels of biologically active prostaglandins by its high level of NAD-dependent 15-hydroxy prostaglandin dehydrogenase (PGDH). In this study, we investigate the effects mediated by CRH receptors on the expression of PGDH in the chorion. We found that both CRH-R1 and CRH-R2 were localized in cultured chorion trophoblast cells, with CRH-R1, R1, R1c, R1e and R1f and CRHR2 isoforms identified in these cells. To block the actions of endogenous CRH and its related peptides, cultured chorion trophoblasts were treated with increasing concentration of -helical CRH 9-41, the nonselective CRH receptor antagonist, which resulted in decreased mRNA and protein expression as well as the activity of PGDH. To investigate the individual role of CRHR1 and CRHR2, cell cultures were treated with the specific CRHR1 antagonist antalarmin and CRHR2 antagonist astressin2B, respectively. The results showed that antalarmin increased whereas astressin2B decreased mRNA and protein expression as well as the activity of PGDH in chrion cells. When the cells were treated with an exclusive CRHR2 agonist, urocortin II, elevated expression and activity of PGDH was exhibited. However, cells treated with either exogenous CRH or urocortin I showed significantly increased PGDH expression, and these effects could be blocked by astressin2B but not by antalarmin. We suggest that, in chorion trophoblast cells, CRHR1 and CRHR2 mediate divergent effects on PGDH expression, and this may provide a precise regulation of PGs levels from chorion to myometrium during pregnancy.