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Regulation of lipoprotein metabolism by estrogen in inbred strains of mice occurs primarily by posttranscriptional mechanisms

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Estrogen protects against developing premature coronary artery disease.However, the mechanism of protective effects of estrogen still remainspoorly understood. One mechanism by which estrogen can have protectiveeffects apppears to be through modulation of plasma lipoproteins. We showedthat the mouse can be used as animal model to study estrogen-mediatedsynthesis and secretion of lipoproteins since, unlike the rat, the mousedoes not up-regulate LDL receptors (Srivastava et al. [4]). Since inbredstrains of mice differ in their genetic background and show differingresponsiveness to dietary lipids, we examined how various inbred strains ofmice respond to estradiol administration, and whether some mouse strainsshow responses similar to rats. 17b-estradiol was administered to male micefrom 15 different inbred strains, and the changes in plasma levels oflipids, apoB, apoAI, and apoE were examined. Total cholesterol decreased inall but one strain, apoAI levels decreased in all but 3 strains while apoBlevels and apoB/apoAI ratios increased in all but 2 strains, suggesting thatin contrast to rats, the apoB-containing lipoproteins increased relative toHDL in all strains of mice examined. Basal and estradiol-induced changes intotal cholesterol were significantly correlated with changes in apoAI, butnot apoB, reflecting the predominance of HDL over other lipoproteins inmouse plasma. The effects of estrogen on plasma apoE levels varied amongvarious inbred strains of mice tested. Plasma apoE levels increased in sevenstrains treated with estrogen, and remained unchanged in the rest. Toexamine whether changes of plasma apoproteins are associated with thechanges in the respective hepatic mRNA levels, apoAI, B and E mRNA werequantified by RNase protection assay. Hepatic apoE mRNA did not showcorrelation with either basal or post treatment plasma apoE levels in any ofthe strains. Similarly, most of the mouse strains did not show correlationof plasma apoAI and apoB levels with the corresponding hepatic mRNA levels.These results suggest that estrogen regulates plasma lipoproteinconcentrations primarily by posttranscriptional mechansims, and there werestrain-related differences in the estrogen-mediated regulation oflipoprotein metabolism.

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Authors and Affiliations

  1. Division of Atherosclerosis, Nutrition and Lipid Research, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, MO, 63110, USA

    Rai Ajit K. Srivastava & Gustav Schonfeld

  2. Searle, Saint Louis, MO, USA

    Elaine S. Krul

  3. Department of Veteran Affairs, VA Medical Center, Indianapolis, IN, 46202, USA

    Renee C. Lin

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  1. Rai Ajit K. Srivastava
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  2. Elaine S. Krul
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  3. Renee C. Lin
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  4. Gustav Schonfeld
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Srivastava, R.A.K., Krul, E.S., Lin, R.C. et al. Regulation of lipoprotein metabolism by estrogen in inbred strains of mice occurs primarily by posttranscriptional mechanisms. Mol Cell Biochem 173, 161–168 (1997). https://doi.org/10.1023/A:1006896131186

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  • DOI: https://doi.org/10.1023/A:1006896131186

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