Prolactin modulation of breast cancer resistance protein and P-glycoprotein expression in a murine model of obesity induced by a high fat diet

MARÍA GUILLERMINA SEDLMEIER; LUCILA CERE; AINELEN ARBOATTI; FLAVIA LAMBERTUCCCI; JUAN A. MONTI; VIVIANA ALICIA CATANIA; MARÍA TERESA RONCO; DANIEL ELEAZAR FRANCÉS

Congreso; REUNION ANUAL SOCIEDAD ARGENTINA DE FISIOLOGIA 2019; 2019

Obesity is a metabolic disease characterized by low-gradeinflammation as well as alterations in serum levels ofdifferent hormones. Prolactin (PRL) is a pleiotropic peptidehormone that participates at different levels to regulatethe metabolism. Obese patients have shown alterations inthe biliary excretion of different exogenous compounds,including therapeutic drugs, affecting theirpharmacokinetics and efficacy. Differential expression ofcanalicular transporters would be involved. Previously, wehave shown that mice fed with High-Fat Diet (HFD)displayed obesity hallmarks and elevated plasma levels ofPRL that were associated with an increased canalicularexpression of the ABC transporters Breast CancerResistance Protein (Bcrp) and P-glycoprotein (P-gp). In thisregard, we suggest that the restoration of plasma levels ofPRL could contribute to normalizing the expression andactivity of transport systems. We aimed to inhibit pituitaryPRL secretion using bromocriptine (Brc) and evaluate thecanalicular expression of ABC transporters in our murinemodel. Five-week-old C57BL/6 mice were fed with regularchow diet (CHOW, n=8) or a 40% high-fat diet (HFD, n=8)for 16 weeks. Mice were injected subcutaneously eitherwith Brc (2 mg/kg or 4 mg/kg, n=4 each group) or vehicle(veh, n=4) for three days. PRL plasma levels weremeasured using an ELISA kit. PRL plasma levels were notmodified when we used the lower dose of Brc, but thedose of 4 mg/kg led to a significant decrease of PRL (-45%;p