Decreased gene expression of 11 beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase in human placenta of patients withpreeclampsia

Cortisol reduces the activity of the PG-inactivating enzyme 15-hydroxyprost aglandin dehydrogenase (PGDH) in human placental cells. The objective was t o investigate a possible relation between 11 beta -hydroxysteroid dehydroge nase type 2 (11 beta -HSD2), converting cortisol to cortisone, and PGDH gen e expression in the placenta of patients with preeclampsia. In placental tissue taken from 20 healthy women with normal pregnancy, 20 p remature babies born after labor before term, and 18 neonates after preecla mptic pregnancy, 11 beta -HSD2 and PGDH messenger RNA (mRNA) expression was determined using quantitative TaqMan real-time PCR and quantitative compet itive PCR. When comparing matched pairs, there were 3-fold lower 11 beta -H SD2/glyceraldehyde-3-phosphate dehydrogenase (11 beta -HSD2/GAPDH) mRNA lev els in placentas of patients with preeclampsia than in controls [0.18 +/- 0 .04 relative units (RU) and 0.61 +/- 0.10 RU, P = 0.0003]. We also found a 2-fold reduction in placental PGDH/GAPDH mRNA concentrations (0.28 +/- 0.15 RU and 0.50 +/- 0.18 RU, P = 0.0003). PGDH and 11 beta -HSD2 mRNA. levels correlated significantly (r = 0.66, P < 0.0001). In term placenta, 11<beta> -HSD2/GAPDH, but not PGDH, showed a significant correlation to birth weight (r = 0.43, P = 0.01) and to placental weight (r = 0.47, P = 0.01). Results could be confirmed by competitive PCR. We conclude that, in preeclampsia, 11 beta -HSD2 mRNA expression is reduced , leading to the known decrease of 11 beta -HSD2 activity. By means of an a utocrine or paracrine mechanism, the diminished conversion of placental cor tisol may lead to reduced PGDH mRNA expression as found in the present stud y.