Regulation of the placental BCRP transporter by PPAR gamma

Identifying regulators of placental breast cancer resistance protein ( BCRP) expression is critical as downregulation of this transporter may increase exposure of the fetus to xenobiotics. Here, we sought to test whether the nuclear receptor peroxisome proliferator-activated receptor gamma ( PPAR gamma) regulates BCRP expression in the placenta. To test this, human BeWo placental choriocarcinoma cells were cultured with the PPAR.. agonist rosiglitazone or the PPAR gamma antagonist T0070907 for 24 h. Messenger RNA ( mRNA) expression of syncytialization markers, GCM1and hCG beta, aswell as BCRP increased with PPAR.. agonist treatment. Conversely, BCRP mRNA and protein expression decreased 30%-50% with PPAR.. antagonist treatment. Rosiglitazone enhanced BCRP protein expression and transport activity, resulting in a20% greater efflux of the substrate Hoechst 33342 compared with control cells. These results suggest that PPAR gamma can upregulate BCRP expression in the placenta, which may be important in understanding mechanisms that protect the fetus from xenobiotic exposure during development.