CLINICAL STUDY Course of placental 11b-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase mRNA expression during human gestation

Background: During human pregnancy, 11b-hydroxysteroid dehydrogenase type 2 (11b-HSD2) plays an important role in protecting the fetus from high maternal glucocorticoid concentrations by converting cortisol to inactive cortisone. Furthermore, 11b-HSD2 is indirectly involved in the regulation of the prostaglandin inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH), because cortisol reduces the gene expression and enzyme activity of PGDH in human placental cells. Objective: To examine developmental changes in placental 11b -HSD2 and PGDH gene expression during the 2nd and 3rd trimesters of human pregnancies. Methods: In placental tissue taken from 20 healthy women with normal pregnancy and 20 placentas of 17 mothers giving birth to premature babies, 11b-HSD2 and PGDH mRNA expression was determined using quantitative real-time PCR. Results: Placental mRNA expression of 11b-HSD2 and PGDH increased signi®cantly with gestational age …r ˆ 0:55; P ˆ 0:0002 and r ˆ 0:42; P ˆ 0:007†: In addition, there was a signi®cant correlation between the two enzymes …r ˆ 0:58; P , 0:0001†: Conclusions: In the course of pregnancy there is an increase in 11b-HSD2 and PGDH mRNA expression in human placental tissue. This adaptation of 11b-HSD2 prevents increasing maternal cortisol concentrations from transplacental passage and is exerted at the gene level. 11b-HSD2 upregulation may also lead to an increase in PGDH mRNA concentrations that, until term, possibly delays myometrial contractions induced by prostaglandins. European Journal of Endocrinology 145 187±192