The ERK1/2 Signaling Pathway Regulates 11beta-Hydroxysteroid Dehydrogenase Type 2 Expression in Human Trophoblast Cells Through a Transcriptional Mechanism.

The ERK1/2 Signaling Pathway Regulates 11beta-Hydroxysteroid Dehydrogenase Type 2 Expression in Human Trophoblast Cells Through a Transcriptional Mechanism. Biol Reprod. 2013 Aug 21; Authors: Guan H, Sun K, Yang K Abstract The placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2; encoded by the HSD11B2 gene) plays a key role in fetal development, but its regulation is incompletely understood. We previously demonstrated that p38 MAPK was a positive regulator of placental 11β-HSD2. However, it remains unknown if the other two MAPKs, ERK1/2 and JNK, were also involved. In the present study, we identified ERK1/2 as an important regulator of placental 11β-HSD2. We showed that inhibition of ERK1/2 with the pharmacological inhibitor U0126 led to a 3-fold increase in 11β-HSD2 activity, protein, and mRNA in primary human placental trophoblast cells. In contrast, the JNK inhibitor SP600125 had no effect. Furthermore, U0126 increased the HSD11B2 promoter activity by 300%, indicating that ERK1/2 regulates placental 11β-HSD2 expression through a transcriptional mechanism. Importantly, siRNA-mediated knockdown of ERK1/2 caused a similar increase in 11β-HSD2 protein. In addition, given that we previously showed that cadmium reduced placental 11β-HSD2 expression via a transcriptional mechanism, but the signal transduction pathways involved remain unclear, we also addressed this question and found that treatment of trophoblast cells with cadmium...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Tags: Biol Reprod Source Type: research