Reversal by triton WR-1339 of ethynyloestradiol-induced hepatic cholesterol esterification

Davis, R.A.; Showalter, R.; Kern, F.

Biochemical Journal 174(1): 45-51


ISSN/ISBN: 0264-6021
PMID: 697762
Accession: 006336794

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Rats treated with ethynyloestradiol have marked hypolipidemia: 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 1-20 mg/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 sulfate/10%-polyacrylamide-gel electrophoresis. The activity of hepatic microsomal acyl-CoA-cholesterol O-acetyltransferase (EC2.3.1.26) was significantly increased by ethynyloestradiol treatment (P < 0.05). This activation caused hepatic cholesteryl esters containing mainly C18:1 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 15 h after Triton WR-1339 administration, serum cholesterol concentrations were increased equally in both control and ethynyloestradiol-treated rats. 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 estrogen activation of hepatic microsomal acyl-CoA-cholesterol O-acyltransferase and restored hepatic cholesteryl ester concentrations to normal values. Ethynyloestradiol and its pharmacological antagonist Triton WR-1339 alter hepatic triacylglycerol secretion via a mechanism associated with changes in hepatic cholesterol esterification.