Hepatic Binding and Internalization of Low Density Lipoprotein-Gold Conjugates in Rats Treated with 17«-Ethinylestradiol

Receptor-mediated hepatic uptake of low density lipoproteins (LDL) conjugated to colloidal gold was studied by perfusion of livers from rats treated for 5 d with 17a-ethinylestradiol . Estrogen treatment resulted in a marked decrease in serum lipid and lipoprotein concentrations . After 15 min of perfusion the conjugate was bound to the hepatic microvilli of both control and estrogen-treated rats ; the estrogen-treated rats showed an 8to 11-fold greater number of membrane-bound conjugates . The conjugates were bound to the membrane receptor by the LDL particle because the gold granules were regularly displaced from the membrane by 20 ± 3.2 nm, the diameter of LDL . Internalization of the conjugate, evident by gold particles in multivesicular bodies, occurred at coated pits at the base of the microvillus where coated vesicles containing a single gold-LDL conjugate were released . After 1 h of perfusion, the livers from the estrogen-treated rats showed all phases of endocytosis and incorporation into multivesicular bodies of the conjugate . After 2 h of perfusion, there was congregation of gold-labeled lysosomes near the bile canaliculi . Gold-LDL conjugates were also observed to bind and be internalized by Kupffer cells and sinusoidal endothelium . These findings in,~icate that estrogen treatment induces hepatic receptors for LDL . The catabolic pathway of binding and endocytosis of the conjugate is similar to that seen in fibroblasts, although slower . Because gold-LDL conjugates were also present in the Kupffer and endothelial cells, the uptake of LDL by the liver involves the participation of more than a