Estrogen-induced cholestasis: pathogenesis and therapeutic implications
Cholestasis syndromes characterised by impairment of bile formation and secretion arecaused by many diseases. Estrogen-induced cholestasis among the cholestasis syndromes is a very common form. Based on the molecular studies of bile formation and transportation, a significant advancement has been achieved in understanding the mechanism of the disease. Estrogen can inhibit bile acids transportation from hepatocytes into bile canaliculi by interfering with the bile salt export pump and multidrug resistance-associated transporter 2 as well. It also inhibits Na+-taurocholate cotransporting polypeptide and Na+-independent organic anion-transporting polypeptides in the basolateral membrane of hepatocytes to interfere with the uptake of bile acids. Thus, co-treatment strategy can be considered which combines nuclear receptor inducers and cAMP enhancer to increase bile acids transporters activities, and the agents to reduce serum estrogen concentration and its receptor binding, and to reduce bile acids in enterohepatic circulation.