Regulation of alpha-foetoprotein gene expression by fatty acids and fibrates

Alpha-foetoprotein (AFP), the major plasma protein in the foetus, is mainly synthesized by yolk sac and foetal liver. It binds polyunsaturated fatty a cids and probably controls their metabolism and action. We investigated the effects of fatty acids and fibrates on expression of the AFP gene using tw o complementary approaches. Treatment with 5-8-11-14 eicosatetraynoic acid (ETYA), an analogue of arachidonic acid, specifically led to lower AFP mRNA levels in cultured rat yolk sac explants whereas treatment with palmitic o r oleic acid did not. Clofibric acid and fenofibrate also gave lower AFP mR NA levels. Transient transfection experiments with HepG2 hepatoma cells sho wed that ETYA and clofibric acid decreased the transcriptional activity of the 7 kb regulatory region of the rat AFP gene. The 330 bp AFP promoter was identified as a target for these down regulating effects.