Regulation of the apolipoprotein AIV gene expression by estrogen differs in rat and mouse.
Previously we have shown that estrogen administration to Sprague Dawley rats and to the inbred C3H/HeJ mouse strain produced different effects on plasma lipoproteins [Srivastava, R. A. K., Baumann, D. & Schonfeld, G. (1993) Eur. J. Biochem. 216, 527-538]. While low-density lipoprotein (LDL) levels fell in rats, they rose in mice. Plasma apoprotein (apo) AI levels and high-density lipoprotein (HDL) cholesterol fell in both species but by much less in mice than in rats. Since apolipoproteins AIV and AII are two other protein constituents of HDL, we wished to test the hypothesis that estrogen would produce different effects on these apoproteins in mice and rats. Male rats and C3H/HeJ mice were administered 17 beta-estradiol at 5 micrograms.g body mass-1.day-1 for six consecutive days. In a separate experiment, castrated male C3H/HeJ mice were administered beta-estradiol [(0.16 micrograms.g body mass-1.day-1 or 5.0 micrograms.g body mass-1.day-1, or testosterone (1 microgram/g)] for 14 days. ApoAIV mRNA levels were determined in total liver, in liver nuclei and in total intestine. Rat hepatic apoAIV mRNA decreased twofold (from 16.5 +/- 3 pg/micrograms total RNA to 7.1 +/- 2.5 pg/micrograms total RNA) while mouse hepatic and nuclear apoAIV mRNA both increased 1.5-2-fold. Intestinal apoAIV mRNA decreased in mice and increased in rats. Testosterone had no effects. Nuclear apoAIV mRNA transcription rates in rat and mouse liver changed little, if at all, indicating that estrogen-induced changes in steady-state levels of apoAIV mRNA were not determined by hepatic transcriptional mechanisms. Both species possessed similar apoAIV mRNA transcription start sites. To assess whether other mouse strains also differed from rats, we surveyed 13 other inbred mouse strains. Some strains increased hepatic apoAIV mRNA, some did not change but, in contrast to rat, no strain experienced a fall in mRNA levels. Estrogen-induced changes in plasma apoAIV levels were not correlated with changes in the levels of hepatic apoAIV mRNA levels. These data indicate that (a) apoAIV mRNA levels are regulated differently by estrogen in mouse and rat livers and intestines, (b) regulation of apoAIV mRNA by estrogen is both mouse strain and tissue specific and (c) regulation of plasma apoAIV is achieved by mechanisms other than those depending on the steady-state levels of hepatic apoAIV mRNA. In contrast with apoAIV mRNA, estrogen decreased hepatic apoAII mRNA both in rat (threefold) and in mouse (twofold) and parallel changes were observed in transcription rates.(ABSTRACT TRUNCATED AT 400 WORDS)
Division of Atherosclerosis, Nutrition and Lipid Research, Washington University School of Medicine, Saint Louis, MO 63110.
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Srivastava
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Kitchens
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Schonfeld
D000818:Animals; D001054:Apolipoproteins A / Q000096:biosynthesis*; D001483:Base Sequence; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D017931:DNA Primers; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009919:Orchiectomy; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013045:Species Specificity; D013739:Testosterone / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D001054:Apolipoproteins A; D017931:DNA Primers; D012333:RNA, Messenger; C022205:apolipoprotein A-IV; D013739:Testosterone; D004958:Estradiol