) TRANSCRIPTIONAL REGULATION OF P-GLYCOPROTEIN BY PROLACTIN IN FEMALE RAT LIVER.

LUCILA CERE; MARÍA GUILLERMINA SEDLMEIER; SEMENIUK MARIANA; LUQUITA MARCELO; DANIEL ELEAZAR FRANCÉS; M. T. RONCO; JUAN PABLO RIGALLI; MARÍA LAURA RUIZ; CATANIA, VIVIANA

Congreso; REUNION ANUAL SOCIEDADES DE BIOCIENCIA 2020; 2020

P-glycoprotein (Pgp), a canalicular transporter encoded by Mdr1aand Mdr1b genes in rodents, plays an important role in the excretionof xenobiotics into bile. Prolactin (PRL) plasma levels are greatlyincreased in lactating females and the classic PRL way of actionimplies interaction with its receptor and activation of Stat5 transcription factor. Previously, we have reported that the activity and proteinexpression of hepatic Pgp were up-regulated in 15 days postpartum(PP) rats, and the same effect was observed in rats after exogenPRL treatment. Aim: To elucidate the mechanism involved in themodulation of hepatic Pgp expression by PRL. Methods: Mdr1a andMdr1b mRNA levels were quantified by qRT-PCR in 1- livers of lactating rats at 15 days PP vs virgin females (VF), 2- primary culturedhepatocytes isolated from female rats. Cells were incubated for 4, 6and 12 h with 0.1 µg/mL PRL (concentration mimicking plasma levels in PP rats) or vehicle. Also, hepatocytes were pre-treated with 5µg/mL actinomycin D (ActD, RNA polymerase II inhibitor) or vehiclefor 30 min, before PRL treatment (0.1 µg/mL) for 12 h or vehicle.Results (% of control, p