Schoof E, Girstl M, Frobenius W, Kirschbaum M, Dörr H G, Rascher W, Dötsch J
Department of Pediatrics, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
J Clin Endocrinol Metab. 2001 Mar;86(3):1313-7. doi: 10.1210/jcem.86.3.7311.
Cortisol reduces the activity of the PG-inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH) in human placental cells. The objective was to investigate a possible relation between 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), converting cortisol to cortisone, and PGDH gene expression in the placenta of patients with preeclampsia. In placental tissue taken from 20 healthy women with normal pregnancy, 20 premature babies born after labor before term, and 18 neonates after preeclamptic pregnancy, 11beta-HSD2 and PGDH messenger RNA (mRNA) expression was determined using quantitative TaqMan real-time PCR and quantitative competitive PCR. When comparing matched pairs, there were 3-fold lower 11beta-HSD2/glyceraldehyde-3-phosphate dehydrogenase (11beta-HSD2/GAPDH) mRNA levels 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 11beta-HSD2 mRNA levels correlated significantly (r = 0.66, P < 0.0001). In term placenta, 11beta-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, 11beta-HSD2 mRNA expression is reduced, leading to the known decrease of 11beta-HSD2 activity. By means of an autocrine or paracrine mechanism, the diminished conversion of placental cortisol may lead to reduced PGDH mRNA expression as found in the present study.
皮质醇可降低人胎盘细胞中前列腺素失活酶15 - 羟基前列腺素脱氢酶（PGDH）的活性。目的是研究2型11β - 羟基类固醇脱氢酶（11β - HSD2，可将皮质醇转化为可的松）与子痫前期患者胎盘组织中PGDH基因表达之间的可能关系。采用定量TaqMan实时PCR和定量竞争性PCR方法，检测了20例正常妊娠健康妇女、20例早产未足月分娩的早产儿以及18例子痫前期妊娠后的新生儿的胎盘组织中11β - HSD2和PGDH信使核糖核酸（mRNA）的表达。在配对比较时，子痫前期患者胎盘组织中11β - HSD2/甘油醛 - 3 - 磷酸脱氢酶（11β - HSD2/GAPDH）mRNA水平比对照组低3倍[分别为0.18±0.04相对单位（RU）和0.61±0.10 RU，P = 0.0003]。我们还发现胎盘PGDH/GAPDH mRNA浓度降低了2倍（分别为0.28±0.15 RU和0.50±0.18 RU，P = 0.0003）。PGDH和11β - HSD2 mRNA水平显著相关（r = 0.66，P < 0.0001）。在足月胎盘中，11β - HSD2/GAPDH（而非PGDH）与出生体重（r = 0.43，P = 0.01）和胎盘重量（r = 0.47，P = 0.01）显著相关。竞争性PCR可证实该结果。我们得出结论，子痫前期患者11β - HSD2 mRNA表达降低，导致已知的11β - HSD2活性下降。通过自分泌或旁分泌机制，胎盘皮质醇转化减少可能导致如本研究中发现的PGDH mRNA表达降低。
