Regulation mechanism of lipid metabolism related gene by estrogen β

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Many reports described that estrogen replacement therapy is effective for preventing postmenopausal women against hyperlipidemia and atherosclerosis. We studied the mechanism underlying this estrogen-dependent lipid metabolism by lipoprotein lipase (LPL) gene promoter analyzes using mouse 3T3-L1 cells. We identified a novel (not consensus) estrogen responsive element, which is located -1856/-1850 of LPL promoter lesion by employing a set of 5 -deletion mutants of LPL-CAT reporter. We also confirmed that this repressive effect of estrogen is mainly mediated by estrogen receptor (ER)-α by co-transfection experiments, whereas ER-β, another estrogen receptor, showed only marginal effect. Next, we investigated effects of estrogen on matrix metalloproteinase activity that has an important role for forming atherosclerotic plaque using human umbilical vein endothelial cells. Zymography demonstrated that six-hour treatment of estrogen inhibited MMP2 activity in a dose-dependent manner. These results suggest that estrogen inhibits hyperlipidemia and atherosclerosis by various mechanisms.