Steroid Regulation of Prostaglandin Dehydrogenase Activity and Expression in Human Term Placenta and Chorio-Decidua in Relation to Labor

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Abstract
NAD1-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) is the key catabolic enzyme controlling levels of biologically active PGs. PGDH is localized to syncytiotrophoblast in placenta, and to trophoblast cells in chorion. To examine the regulation of PGDH by steroids and to determine any changes with labor, we obtained pla- centa and chorion from term elective cesarean section or spontaneous delivery and isolated trophoblast cells using a Percoll density gradi- ent. Cells were treated with varying concentrations of cortisol, pro- gesterone, the synthetic progestins R5020, and medroxyprogesterone acetate with or without RU486 or the specific progesterone receptor antagonist, onapristone, and the 3b-hydroxysteroid dehydrogenase inhibitor, trilostane. The activity of PGDH was assessed by measure- ment of 13,14-dihydro-15-keto-PGF2a. PGDH messenger ribonucleic acid was quantified by in situ hybridization and computerized image analysis. The basal output of 13,14-dihydro-15-keto-PGF2a was lower in placenta or chorion collected at spontaneous labor than in that ob- tained at elective cesarean section. Cortisol had a significant dose- dependent inhibitory effect on PGDH activity in both placental and chorion trophoblast cells and significantly decreased levels of PGDH messenger ribonucleic acid. Responses were similar between tissues from laboring and nonlaboring women. PGDH activity was increased by R5020 and medroxyprogesterone acetate and was inhibited by RU486, onapristone, and trilostane. We conclude that cortisol inhibits PGDH activity and expression and that progestagens increase PGDH activity in human chorion and placenta. (J Clin Endocrinol Metab 84: 291-299, 1999)

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