Activation of the Liver X Receptor (LXR) in the mouse mammary gland promotes lactogenic phenotype and inhibits involution- associated features

EMILIA BOGNI; DIEGO GRINMAN; ADALI PECCI; EDITH C. KORDON

Simposio; SISTAM 2018; 2018

The final fate for the luminal epithelial cell in the mammary gland is the lactogenic phenotype, which is induced by hormones, mainly glucocorticoids and prolactin, induce the expression of genes involved in lipid homeostasis. After weaning the mammary gland undergoes involution, a complex process of controlled apoptosis and tissue remodeling that involves the expression and release of inflammatory and proapoptotic factors. Liver-X-Receptors (LXR) are ligand- dependent transcription factors that upon activation by cholesterol metabolites, and inhibits a number of inflammatory molecules. It has been recently found that LXRα is expressed in the mammary epithelium during lactation, where is an important regulator of milk lipid transport. Our results show that incubation with the LXRα agonist GW3965 induced expression of the milk protein beta-casein and the anti-inflammatory regulatortristetraprolin (TTP) in the murine mammary cell line HC11. In addition, treatment of weaned female mice with GW3965 for 96h resulted in the increase of TTP levels and decreased expression of cytokines, as IL-6 and TNFɑ, in the mammary tissue. Besides,morphologically, mammary glands of GW3965 treated mice showed signs of delayed involution as maintained alveolar structures, which were rare in control animals treated with vehicle. Therefore, based on our data, we propose that activation of LXRα is relevant for maintaining the lactating phenotype. Our results suggest that the activation of this receptor would block the rise of inflammatory cytokines, which lead the mammary involution process that occurs after weaning. More experiments are required to determine the mechanisms underlying the observed effects.