In vitro modulation of the expression of 15-hydroxyprostaglandin dehydrogenase by trophoblast differentiation

OBJECTIVE: Our goal was to determine the expression and activity of 15-hydr oxy-prostaglandin dehydrogenase, a prostaglandin-metabolizing enzyme, in di fferentiating trophoblasts in vitro. STUDY DESIGN: Cytotrophoblasts from placentas of term healthy women were cu ltured in either Ham's-Waymouth medium, which hinders the process of cytotr ophoblast differentiation, or medium 199, which facilitates differentiation into syncytiotrophoblasts. 15-Hydroxy-prostaglandin dehydrogenase expressi on was determined with Western immunoblotting, and activity was measured by a specific enzyme immunoassay of 13,14-dihydro-15-keto prostaglandin F-2 a lpha, an inactive product of 15-hydroxy-prostaglandin dehydrogenase activit y. RESULTS: The expression and activity of 15-hydroxy-prostaglandin dehydrogen ase were enhanced during trophoblast differentiation and were higher in cel ls grown in medium 199 than in those grown in Ham's-Waymouth medium. 8-Brom o-cyclic adenosine monophosphate, which stimulates prostaglandin H synthase -2 expression, diminished the expression and activity of 15-hydroxy-prostag landin dehydrogenase in concentration- and time-dependent manners. CONCLUSIONS: 15-Hydroxy-prostaglandin dehydrogenase expression and activity are regulated during trophoblast differentiation and by cyclic adenosine m onophosphate. Coordinated expression of 15-hydroxy-prostaglandin dehydrogen ase and prostaglandin H synthase-2 contributes to the regulation of prostag landin release from trophoblasts.