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

Objective: Our goal was to determine the expression and activity of 15-hydroxy-prostaglandin dehydrogenase, a prostaglandin-metabolizing enzyme, in differentiating trophoblasts in vitro. Study Design: Cytotrophoblasts from placentas of term healthy women were cultured in either Ham’s-Waymouth medium, which hinders the process of cytotrophoblast differentiation, or medium 199, which facilitates differentiation into syncytiotrophoblasts. 15-Hydroxy-prostaglandin dehydrogenase expression was determined with Western immunoblotting, and activity was measured by a specific enzyme immunoassay of 13,14-dihydro-15-keto prostaglandin F2α , an inactive product of 15-hydroxy-prostaglandin dehydrogenase activity. Results: The expression and activity of 15-hydroxy-prostaglandin dehydrogenase were enhanced during trophoblast differentiation and were higher in cells grown in medium 199 than in those grown in Ham’s-Waymouth medium. 8-Bromo-cyclic adenosine monophosphate, which stimulates prostaglandin H synthase-2 expression, diminished the expression and activity of 15-hydroxy-prostaglandin dehydrogenase in concentration- and time-dependent manners. Conclusions: 15-Hydroxy-prostaglandin dehydrogenase expression and activity are regulated during trophoblast differentiation and by cyclic adenosine monophosphate. Coordinated expression of l5-hydroxy-prostaglandin dehydrogenase and prostaglandin H synthase-2 contributes to the regulation of prostaglandin release from trophoblasts. (Am J Obstet Gynecol 1999;180:690-5.)