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KMID : 0667720000370000409
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Report Natlonal Institute of Health
2000 Volume.37 No. 0 p.409 ~ p.410
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Regulation of Cholesterol Homeostasis-Related Gene Expression by High Fat diet and Estrogen
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Abstract
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Although many studies have reported the beneficial effects of estrogen on cardiovascular disease, no clear mechansim has been proposed how estrogen regulates the level of cholesterol and the expression of genes related with cholesterol homeostasis. Sprague Dawley rats were divided into normal fat diet and high fat diet groups. The high fat diet was made by adding cholesterol (2%), lard oil (5%), cholic acid (0.3%). 6-propyl-2-thiouracil (0.1%) to the pulverized normal diet and mixing. After 40 days feeding, each diet group was divided into propylene glycol treated groups (N: normal fat diet group. HE: high fat diet group) and estrogen treated groups (NE: normal fat diet and estrogen. HE: high fat diet and estrogen). 17α-ethinyl estradiol(EE) was the treated form of estrogen and given at 10mg/kg/per day for 4 days.
High fat feeding increased the levels of plasma total cholesterol and LDL-C and the activities of plasma GOT and GPT and induced the fatty liver with the increased hepatic mRNA levels of cytochrome P450 2EI and inducible Nitric Oxide Synthase. Estrogen treatment decreased the level of total cholesterol and LDL-C as well as the damage of liver.
High fat diet decreased the mRNA levels of LDLR and HMGR by 45% and 20% respectively, while it did not alter that of 7α-hydroxylase (7α-OHase). Treatment of EE recovered the LDL receptor (LDLR) mRNA to that of N. However EE did not change HMG-CoA reductase and rather decreased 7α-OHase mRNA. We experimented that the expression pattern of estrogen receptor-α (ER-α), chicken ovalbumin upstream promoter- transcription factor (COUP-TF), and hepatocyte growth factor (HGF), which may be involved in LDLR expression. ER-α mRNA level was reduced in HF and HE but wasn´t significantly different from normal fat group and COUP-TF mRNA level was not influenced by diet nor estrogen. HGF mRNA level was induced by high fat diet and down-regulated in NE.
Taken together, we found estrogen improved lipid profiles by coordinative regulation of LDL receptor and 7α-OHase and reduced the hypercholesterolemia-induced expression of HGF. It is necessary to study further to understand the regulation of LDLR and 7α-OHase in cholesterol metabolism, and relationship between ER-α and HGF.
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KEYWORD
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