17 alpha-ethinylestradiol increases transcytosis of asialoglycoproteins in rat liver.

Abstract

We have measured the hepatobiliary transcytosis of asialofetuin (ASF) and low density lipoprotein (LDL) in rats following treatment with 5 mg of 17 alpha-ethinylestradiol/kg of body weight for 3 days. The rate of appearance of both ligands in bile was increased 5-fold in estradiol-treated rats compared with controls. In contrast, no increase was observed in the transcytosis of dimeric IgA. The majority of the ASF recovered from the bile of estradiol-treated rats was undegraded, indicating transcytic delivery rather than lysosomal discharge. No increase in the rate of endocytosis of ASF was observed. When transcytosis of 125I-LDL was measured in the presence of excess ASF the rate decreased by approximately 70%. Moreover, sialidase treatment of LDL in vitro increased the biliary appearance of LDL 2-fold in estradiol-treated rats, suggesting that the effect of estradiol on both ligands was mediated via the asialoglycoprotein receptor. We conclude that 17 alpha-ethinylestradiol increases the transcytosis of ASF and LDL through mechanisms that alter the intracellular trafficking of the asialoglycoprotein receptor.