Effect of 17 alpha-ethinylestradiol on the catabolism of high-density lipoprotein apolipoprotein A-I in the rat.
The in vivo metabolism and tissue sites of catabolism of high-density lipoproteins (HDL), labelled specifically in the apolipoprotein (apo) A-I moiety, were studied in rats treated with 17 alpha-ethinylestradiol (EE) for 5 days. Apo A-I was labelled either with O-(4-diazo-3-[125I]iodobenzoyl)sucrose, a non-degradable labelling compound, or with 131ICl. It was found that EE treatment decreases the serum cholesterol concentration to 10 mg/dl and stimulates the serum decay of apo A-I labelled HDL. The latter effect could be attributed to an increased catabolism of apo A-I labelled HDL in the liver. The increased rates of the serum decay and tissue uptake of apo A-I labelled HDL in EE-treated rats were not affected by a bolus injection of unlabelled human low-density lipoprotein (LDL), administered at the time of the injection of the labelled HDL. When the serum cholesterol concentration was raised to physiological levels by a bolus injection of unlabelled rat HDL, both the serum decay and the tissue uptake of apo A-I labelled HDL were almost completely restored to conditions encountered in control animals. In vitro binding experiments showed that liver membranes obtained from EE-treated rats demonstrated a 6-fold increased specific binding of human 125I-LDL, but virtually unchanged specific binding of rat 125I-HDL, as compared with liver membranes obtained from control rats. It is concluded that rat HDL apo A-I catabolism is hardly mediated by the apo B/E receptor induced by EE treatment.
D000818:Animals; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000378:metabolism*; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D008075:Lipoproteins, HDL; D004997:Ethinyl Estradiol