Fig. 2.

ERα signaling from the membrane suppresses the expression of genes involved in lipid synthesis. Estrogen-triggered signaling in liver through the ERα receptor at the membrane activates a kinase cascade, including protein kinase A/liver kinase B (LKB) signaling to AMP kinase (AMPK) activation. AMPK phosphorylates sterol regulatory element-binding protein 1 (SREBF-1), thereby preventing its NH₂-terminal cleavage by S1 or S2 proteases in Golgi. Failure of SREBF-1 processing prevents nuclear translocation of the transcription factor. Therefore, SREBF-1 is sequestered in cytoplasm and cannot augment the expression of mRNAs involved in lipid synthesis.