Hepatic binding and internalization of low density lipoprotein-gold conjugates in rats treated with 17 alpha-ethinylestradiol.

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Abstract
Receptor-mediated hepatic uptake of low density lipoproteins (LDL) conjugated to colloidal Au was studied by perfusion of livers from rats treated for 5 [day] with 17.alpha.-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 control and estrogen-treated rats; the estrogen-treated rats showed an 8- to 11-fold greater number of membrane-bound conjugates. The conjugates were bound to the membrane receptor by the LDL particle because the Au granules were regularly displaced from the membrane by 20 .+-. 3.2 nm, the diameter of LDL. Internalization of the conjugate, evident by Au 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 purfusion, 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 Au-labeled lysosomes near the bile canaliculi. Au-LDL conjugates were also observed to bind and be internalized by Kupffer cells and sinusoidal endothelium. Estrogen treatment induced hepatic receptors for LDL. The catabolic pathway of binding and endocytosis of the conjugate is similar to that seen in fibroblasts, although slower. Because Au-LDL conjugates were also present in the Kupffer and endothelial cells, the uptake of LDLA by the liver involves the participation of more than a single cell type.