The role of the aryl hydrocarbon receptor and the liver X receptor in gene regulation and metabolic homeostasis

摘要: The aryl hydrocarbon receptor (AhR) is a PAS domain transcriptional factor also known as the i§dioxin receptori¨ or i§xenobiotic receptor.i¨ My thesis work has uncovered an endobiotic role for AhR in hepatic steatosis and other metabolic functions. Activation of induced spontaneous steatosis, which characterized by accumulation triglycerides. steatotic effect was likely due to combined upregulation fatty acid translocase CD36/FAT, suppression oxidation, inhibition export triglycerides, increase mobilization peripheral fat. Promoter analysis established CD36 novel target AhR. Moreover, agonist inhibited mice deficient CD36. Results from this study may help establish its attractive targets intervention liver disease. X receptors (LXRs), both ƒN ƒO isoforms, are nuclear identified sterol sensors that modulate cholesterol lipid metabolism homeostasis. In second part my research, I report LXR-mediated mechanism androgen deprivation. Genetic pharmacological activation (LXR) vivo lowered androgenic activity inducing hydroxysteroid sulfotransferase 2A1 (SULT2A1), enzyme essential deactivation androgens. LXR expression steroid sulfatase (STS) prostate, have helped prevent local conversion sulfonated androgens back active metabolites. At physiological level, androgen-dependent prostate regeneration castrated mice. Treatment with agonists proliferation cancer cells LXR- SULT2A1-dependent manner. ability LXRs regulate makes them therapeutic treatment prevention hormone-dependent cancer. Taken together, revealed functions It hoped understandings these two management disease humans.