Expression of 11‐beta hydroxysteroid dehydrogenase type 2 in the murine placenta and its regulation in cultured placental trophoblasts

Abstract

HSD2 is a microsomal enzyme responsible for the oxidation of 11-hydroxy glucocorticoids (GCs) to their biologically inert 11-keto forms in peripheral tissues. Placental HSD2 activity plays a key role in protecting the fetus from high levels of maternal GCs. Prenatal exposure to high levels of GCs has been linked the fetal programming of several adult cardiovascular and metabolic diseases. We examined HSD2 protein levels in the murine placenta during gestation and explored its regulation in cultured murine placental trophoblast cells (SM-10 cell line). Immunoblot analysis for HSD2 protein was performed on pooled placentas obtained from C57BL/6 mice on gestational days 9, 12, 14, or 18 (n=4 litters for each time point). Normalized placental HSD2 protein levels increased with gestational age, and were approximately two-fold higher on day 18 as compared to day 9. The effect of inflammatory cytokines on HSD2 protein levels was also examined in SM-10 cells cultured in the presence of TNF-alpha (10ng/mL) or IL-1 beta (10ng/mL) for 1, 2, or 24 hours. HSD2 was down-regulated in a time-dependent manner by the inflammatory cytokines. The reduction of HSD2 levels by these cytokines may provide a potential link between placental inflammation and fetal programming. These data demonstrate that SM-10 cells provide a useful model in which to study the regulation of HSD2 in the murine placenta.