Hepatic handling of bile salts and protein in the rat during intrahepatic cholestasis

Abstract

17 α-Ethynyl estradiol-induced cholestasis was used to study the relationship of protein to bile salt transport in liver. The biliary secretion of horseradish peroxidase was unaltered in treated animals despite a 56% reduction in bile flow. Cytochemistry confirmed that estradiol caused no alteration in the handling of tracer. In a second study, the peak biliary secretion of [14C]taurocholate was reduced by ~46% in treated animals. The kinetics of 125I-cholylglycylhistamine, a bile salt derivative, were identical to those of taurocholate in control and cholestatic animals. Taurocholate and cholylglycylhistamine secretion were markedly reduced in control animals during competition with unlabeled taurocholate. Quantitative electron microscopic autoradiography with 125I-cholylglycyihistamine revealed a high concentration of grains over the endoplasmic reticulum and the Golgi complex including associated lysosomes and vesicles. These data demonstrate that estradiol markedly inhibits bile salt transport, but not vesicular transport of horseradish peroxidase. Furthermore, estradiol may alter the movement of bile salts through these organelles.