RETINOID-X-RECEPTOR (RXR-ALPHA) GENE-EXPRESSION IS REGULATED BY FATTY-ACIDS AND DEXAMETHASONE IN HEPATIC CELLS

This work describes the molecular mechanism of fatty acid and hormonal modulation of retinoid X receptor (RXR alpha) in rat liver. We examin ed the effects of different fatty acids (myristic-, stearic-, linoleni c-, oleic-, arachidonic- and tetradecylthioacetic acid (TTA)) and the synthetic glucocorticoid dexamethasone on RXR alpha mRNA and protein s teady-state levels in hepatoma cells and cultured hepatocytes. Fatty a cids induced the RXR alpha gene expression where TTA showed the most i nductive effect (three-fold induction). Dexamethasone alone resulted i n a stronger induction (up to seven-fold in hepatocytes), and in combi nation with fatty acids, an additive or synergistic effect was observe d. The RXR alpha protein level in cultured hepatocytes showed a simila r pattern of regulation, with a slight inductive effect of fatty acids and an additive or synergistic effect was observed in combination wit h dexamethasone. Our results indicate that the RXR alpha gene expressi on is under distinct regulation by fatty acids and dexamethasone acid which strongly suggests a coupling with the Lipid metabolizing system and the retinoid signaling pathway.