Metabolism of chylomicron cholesterol is delayed by estrogen. An in vivo study in the rat

In order to test the effects of estrogen on the clearance of cholesterol of dietary origin from the blood and its elimination from the body via the bi le in an in vivo animal model, the fate of radioactivity from intravenously injected [H-3]cholesterol-labeled chylomicrons was investigated in the rat . The labeled lipoproteins were administered intrajugularly to male rats pr eviously given 17 alpha ethinyl estradiol or the vehicle only, and the remo val of the radioactivity from the blood and its uptake by the liver and sec retion into bile was determined. Experiments were carried out in animals wi th or without prior drainage (20 hr) of the pool of bile acids in the enter ohepatic circulation, to take account of the different demands of the liver for cholesterol in the two conditions. In rats without biliary drainage, e strogen treatment decreased the rate of removal of radioactivity from the b lood by about 30% and the recovery of cholesterol in the liver by about 50% in the first 30 min after injection of the labeled chylomicrons. After bil iary drainage, however, the recovery of label in the liver after 90 min was similar in estrogen-treated and control animals, although its secretion in to bile was markedly reduced in the estrogen-treated group (total biliary s ecretion in 90 min was 26% of the value found in control rats). In addition , the apolipoprotein E (aopE) content of the serum total lipoproteins was m arkedly reduced by estrogen. These results provide direct evidence indicati ng that estrogen retards the elimination of dietary cholesterol from the bo dy via the bile in the rat, and this is likely to be mainly due to a reduce d level of apoE in chylomicrons. In view of this, we suggest that the hypot hesis that estrogen increases the hepatic uptake of chylomicron cholesterol , and its excretion in the bile during contraceptive and hormone replacemen t therapy should he re-examined.