Cellular and subcellular distribution of 125I-labeled very low density lipoproteins in the liver of normal and estrogen-treated rabbits.

Cholesterol and apo-E-rich very low density lipoproteins (VLDL) are rapidly removed from the circulation by the liver, and estrogen treatment enhances this uptake. The purpose of this study was to determine the cellular site(s) of cholesterol-rich VLDL uptake and the effect of estrogen on the cellular and subcellular distribution of these lipoproteins. (125)I-labeled VLDL, obtained from cholesterol-fed rabbits, were perfused through the isolated rabbit livers for 1/2, 1, 2, and 4 minutes, followed by a 5-minute chase. In both normal and estrogen-treated animals the uptake of VLDL increased linearly with time; however, this uptake was markedly increased by estrogen treatment. Lightmicroscopic autoradiography demonstrated that the majority (70-76%) of the label was localized in the hepatocytes of both normal and estrogen-treated animals. The remaining label was distributed in sinusoidal space (16-20%), littoral cells (6-7%), and bile ducts and large vessels (1-2%). Electron-microscopic autoradiography revealed that at earlier time points (125)I-VLDL were associated with the hepatocyte cell boundary. At later time points the majority of the labeled product (68-72%) was associated with hepatocyte cytoplasm. The estrogen-treated animals at earlier time points, however, had a relatively higher proportion (50%) of grains in the hepatocyte cytoplasm as compared with controls (21%).These findings indicate that 1) the parenchymal cells are primarily responsible for the uptake of cholesterol-rich VLDL, 2) internalization of the labeled product is preceded by its accumulation at the cell boundary, and 3) the mechanism of uptake and processing of the lipoproteins is similar in both normal and estrogen-treated animals but appears to be enhanced in the estrogen-treated animals.