Steroid regulation of prostaglandin dehydrogenase activity and expression in human term placenta and chorio-decidua in relation to labor

NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) is the key ca tabolic enzyme controlling levels of biologically active PGs. PGDH is local ized to syncytiotrophoblast in placenta, and to trophoblast cells in chorio n. To examine the regulation of PGDH by steroids and to determine any chang es with labor, we obtained placenta and chorion from term elective cesarean section or spontaneous delivery and isolated trophoblast cells using a Per coll density gradient. Cells were treated with varying concentrations of co rtisol, progesterone, the synthetic progestins R5020, and medroxyprogestero ne acetate with or without RU486 or the specific progesterone receptor anta gonist, onapristone, and the 3 beta-hydroxysteroid dehydrogenase inhibitor, trilostane. The activity of PGDH was assessed by measurement of 13,14-dihy dro-15-keto-PGF(2 alpha). PGDH messenger ribonucleic acid was quantified by in situ hybridization and computerized image analysis. The basal output of 13,14-dihydro-15-keto-PGF(2 alpha) was lower in placent a or chorion collected at spontaneous labor than in that obtained at electi ve cesarean section. Cortisol had a significant dose-dependent inhibitory e ffect on PGDH activity in both placental and chorion trophoblast cells and significantly decreased levels of PGDH messenger ribonucleic acid. Response s were similar between tissues from laboring and nonlaboring women. PGDH ac tivity was increased by R5020 and medroxyprogesterone acetate and was inhib ited by RU486, onapristone, and trilostane. We conclude that cortisol inhib its PGDH activity and expression and that progestagens increase PGDH activi ty in human chorion and placenta.