Davis R A, Showalter R, Kern F
Biochem J. 1978 Jul 15;174(1):45-51. doi: 10.1042/bj1740045.
serum cholesterol is decreased to 5%, triacylglycerol to 10% and phospholipid to 70% of control concentrations. Loss of serum cholesterol follows an exponential decay, with a half-life of 1.13+/-0.09 days. After 4 days of treatment, serum cholesterol concentrations remain relatively constant (ranging from 1 to 20mg/100ml) for at least 30 days. There is a concomitant 20-fold decrease in the d<1.21 fraction of serum proteins and a similar decrease in serum apolipoproteins as measured by sodium dodecyl sulphate/10%-polyacrylamide-gel electrophoresis. The activity of hepatic microsomal acyl-CoA-cholesterol O-acetyltransferase (EC 2.3.1.26) was significantly increased by ethynyloestradiol treatment (P<0.05). This activation caused hepatic cholesteryl esters containing mainly C(18:1) fatty acids to increase linearly as serum cholesterol concentrations decreased (r=0.9675, P<0.001). Triton WR-1339, a non-ionic detergent that inhibits lipoprotein catabolism, was used to estimate hepatic lipid secretion by measuring the increment in serum lipids after its administration. At 15h after Triton WR-1339 administration, serum cholesterol concentrations were increased equally in both control and ethynyloestradiol-treated rats. In contrast, the increment of serum triacylglycerol of treated rats was 40% of that found in control rats, indicating that ethynyloestradiol inhibits hepatic triacylglycerol secretion. Triton WR-1339 inhibited the oestrogen activation of hepatic microsomal acyl-CoA-cholesterol O-acyltransferase and restored hepatic cholesteryl ester concentrations to normal values. These data suggest that ethynyloestradiol and its pharmacological ;antagonist' Triton WR-1339 alter hepatic triacylglycerol secretion via a mechanism associated with changes in hepatic cholesterol esterification.
血清胆固醇降至对照浓度的5%，三酰甘油降至10%，磷脂降至70%。血清胆固醇的减少呈指数衰减，半衰期为1.13±0.09天。治疗4天后，血清胆固醇浓度至少30天保持相对恒定（范围为1至20mg/100ml）。通过十二烷基硫酸钠/10%-聚丙烯酰胺凝胶电泳测定，血清蛋白d<1.21部分伴随有20倍的下降，血清载脂蛋白也有类似程度的下降。乙炔雌二醇治疗显著增加了肝微粒体酰基辅酶A-胆固醇O-乙酰转移酶（EC 2.3.1.26）的活性（P<0.05）。这种激活导致主要含有C(18:1)脂肪酸的肝胆固醇酯随着血清胆固醇浓度的降低而线性增加（r=0.9675，P<0.001）。Triton WR-1339是一种抑制脂蛋白分解代谢的非离子去污剂，通过测量给药后血清脂质的增加来估计肝脂质分泌。在给予Triton WR-1339 15小时后，对照大鼠和乙炔雌二醇治疗的大鼠血清胆固醇浓度均有相同程度的增加。相比之下，治疗大鼠血清三酰甘油的增加量是对照大鼠的40%，这表明乙炔雌二醇抑制肝三酰甘油分泌。Triton WR-1339抑制了肝微粒体酰基辅酶A-胆固醇O-酰基转移酶的雌激素激活，并使肝胆固醇酯浓度恢复到正常值。这些数据表明，乙炔雌二醇及其药理学“拮抗剂”Triton WR-1339通过与肝胆固醇酯化变化相关的机制改变肝三酰甘油分泌。
