GENE-TRANSCRIPTION OF THE RETINOID-X-RECEPTOR-ALPHA (RXR-ALPHA) IS REGULATED BY FATTY-ACIDS AND HORMONES IN RAT HEPATIC CELLS

This work describes the molecular mechanisms of fatty acid and hormona l modulations of the retinoid X receptor alpha (RXR alpha) in rat live r cells. We examined the effects of different fatty acids (myristic, s tearic, oleic, linolenic, and arachidonic acids, EPA, and the peroxiso mal proliferator TTA) and several hormones (the glucocorticoid analogu e dexamethasone, insulin, and retinoic acid) on the RXR alpha mRNA and protein levels in rat hepatoma cells and cultured hepatocytes. The fa tty acids induced the RXR alpha gene expression resulting in up to 3-f old induction. Dexamethasone alone induced the mRNA level and, in comb ination with fatty acids, an additive or synergistic effect was observ ed. The dexamethasone-increased mRNA level was obliterated by insulin. The same pattern of regulation of the protein level was observed when determined in cultured hepatocytes, but the induced protein level sho wed a lower magnitude of stimulation than tile mRNA level. This could indicate a post-transcriptional modulation of the RXR alpha gene expre ssion. Time course studies showed a maximal induction of mRNA and prot ein levels after 18 h and 48 h, respectively. Our results uniformly sh ow that the RXR alpha gene expression is under distinct regulation by fatty acids and hormones which suggests a coupling with the lipid meta bolizing system and the hormonal signaling pathway.