Increased binding of low density lipoprotein to liver membranes from rats treated with 17 alpha-ethinyl estradiol.

Pharmacologic doses of 17a-ethinyl estradiol have been reported to cause a marked lowering of plasma lipoprotein levels in the rat. The drop in plasma low density lipoprotein (LDL) is associated with enhanced uptake of LDL by the liver. In the current studies, we show that membranes prepared from livers of ethinyl estradiol-treated rats exhibit a 3to lo-fold increase in saturable binding sites for human lz51-LDL. These binding sites resembled the LDL receptors previously described in extrahepatic human, mouse, and bovine cells in that they: 1) showed a marked preference for human LDL as opposed to human high density lipoprotein (HDL); 2) required calcium; 3) failed to bind LDL in which the lysine residues had been acetylated or methylated in uitro; and 4) were destroyed by pronase. Hepatic uptake of intravenously administered human lz51-LDL was la-fold higher in estradiol-treated rats as compared with controls. Uptake of lz51-LDL was competitively inhibited by unlabeled human LDL, but not by human HDL. Moreover, methylated human lz51-LDL, which did not bind to the LDL site on membranes, was taken up by the liver in uiuo at a lo-fold lower rate than “‘1-LDL. These data suggest that the lz51-LDL membrane binding site that was detected in vitro mediated the uptake of lz51-LDL in uiuo. Livers of untreated and ethinyl estradiol-treated rats also exhibited a saturable binding site for human 12’1HDL. This site bound human HDL much more avidly than human LDL. HDL binding was not increased by ethinyl estradiol treatment, did not require calcium, and was not destroyed by pronase. Whether the “‘ILDL and 1251-HDL binding sites function as hepatic lipoprotein receptors in untreated rats is not yet known.