Effects of Ethinylestradiol-Induced Cholestasis on Bile Flow and Biliary Excretion of Estradiol and Estradiol Glucuronide by the Rat

The effects of ethinylestradiol treatment on bile flow and biliary excretion of bromsulfophthalein, estradiol, and estradiol glucuronide in the rat were studied. One day following 9 days of 0.5 mg of ethinylestradiol treatment, bile duct cannulation and femoral vein catheterization were carried out. From that time until the end of study, bile flow was strikingly reduced in the estrogen-treated animals to less than 50% of that in the control group. One day following surgery, studies of biliary excretion were performed revealing a markedly diminished biliary excretion of radioactivity from intravenously administered tracer doses of both estradiol and estradiol glucuronide in the treated animals. The effect of estrogen treatment on bile flow and estrogen excretion in the bile is similar to that previously observed for bromsulfophthalein clearance. Possible mechanisms of estrogen action and implications in human estrogen-induced cholestasis are discussed.