Regulation of lipoprotein metabolism by estrogen in inbred strains of mice occurs primarily by posttranscriptional mechanisms.
Estrogen protects against developing premature coronary artery disease. However, the mechanism of protective effects of estrogen still remains poorly understood. One mechanism by which estrogen can have protective effects appears to be through modulation of plasma lipoproteins. We showed that the mouse can be used as animal model to study estrogen-mediated synthesis and secretion of lipoproteins since, unlike the rat, the mouse does not up-regulate LDL receptors (Srivastava et al. [4]). Since inbred strains of mice differ in their genetic background and show differing responsiveness to dietary lipids, we examined how various inbred strains of mice respond to estradiol administration, and whether some mouse strains show responses similar to rats. 17beta-estradiol was administered to male mice from 15 different inbred strains, and the changes in plasma levels of lipids, apoB, apoAI, and apoE were examined. Total cholesterol decreased in all but one strain, apoAI levels decreased in all but 3 strains while apoB levels and apoB/apoAI ratios increased in all but 2 strains, suggesting that in contrast to rats, the apoB-containing lipoproteins increased relative to HDL in all strains of mice examined. Basal and estradiol-induced changes in total cholesterol were significantly correlated with changes in apoAI, but not apoB, reflecting the predominance of HDL over other lipoproteins in mouse plasma. The effects of estrogen on plasma apoE levels varied among various inbred strains of mice tested. Plasma apoE levels increased in seven strains treated with estrogen, and remained unchanged in the rest. To examine whether changes of plasma apoproteins are associated with the changes in the respective hepatic mRNA levels, apoAI, B and E mRNA were quantified by RNase protection assay. Hepatic apoE mRNA did not show correlation with either basal or post treatment plasma apoE levels in any of the strains. Similarly, most of the mouse strains did not show correlation of plasma apoAI and apoB levels with the corresponding hepatic mRNA levels. These results suggest that estrogen regulates plasma lipoprotein concentrations primarily by posttranscriptional mechanisms, and there were strain-related differences in the estrogen-mediated regulation of lipoprotein metabolism.
Srivastava
R A
RA
Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
Krul
E S
ES
Lin
R C
RC
Schonfeld
G
G
D000818:Animals; D016632:Apolipoprotein A-I / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D001055:Apolipoproteins B / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D001057:Apolipoproteins E / Q000097:blood / Q000187:drug effects / Q000235:genetics; D001059:Apoproteins / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000187:drug effects* / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D001059:Apoproteins; D004967:Estrogens; D008055:Lipids; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D004958:Estradiol; D002784:Cholesterol