17 alpha-ethinylestradiol increases transcytosis of asialoglycoproteins in rat liver.
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.
Burgess
J W
JW
Heart Research Institute, Camperdown, NSW, Sydney, Australia.
Stanley
K K
KK
D000818:Animals; D001212:Asialoglycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001652:Bile Ducts / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D060748:Fetuins; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000302:isolation & purification / Q000378:metabolism*; D000509:alpha-Fetoproteins / Q000302:isolation & purification / Q000378:metabolism*
D001212:Asialoglycoproteins; D060748:Fetuins; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D000509:alpha-Fetoproteins; C017029:asialofetuin; D004997:Ethinyl Estradiol; D002784:Cholesterol