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. 1986 Feb;83(3):792–796. doi: 10.1073/pnas.83.3.792

Increased mRNA for low density lipoprotein receptor in livers of rabbits treated with 17 alpha-ethinyl estradiol.

P T Ma, T Yamamoto, J L Goldstein, M S Brown
PMCID: PMC322951  PMID: 2418443

Abstract

Pharmacologic doses of 17 alpha-ethinyl estradiol are known to increase the number of low density lipoprotein (LDL) receptors in livers of rats, thereby producing a profound fall in plasma cholesterol levels. We now report that ethinyl estradiol exerts the same effect in livers of male and female rabbits and that the increase in receptor number is correlated with a 6- to 8-fold increase in the levels of receptor mRNA. Receptor protein was measured by ligand blotting, and mRNA levels were measured by a quantitative solution hybridization/S1 nuclease protection assay using uniformly 32P-labeled single-stranded cDNA probes. These experiments demonstrate that pharmacologic induction of the mRNA for the LDL receptor in liver can lead to increased LDL receptor levels and a fall in plasma cholesterol in experimental animals.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brown M. S., Goldstein J. L. Lipoprotein receptors in the liver. Control signals for plasma cholesterol traffic. J Clin Invest. 1983 Sep;72(3):743–747. doi: 10.1172/JCI111044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown M. S., Kovanen P. T., Goldstein J. L. Regulation of plasma cholesterol by lipoprotein receptors. Science. 1981 May 8;212(4495):628–635. doi: 10.1126/science.6261329. [DOI] [PubMed] [Google Scholar]
  3. Carew T. E., Pittman R. C., Steinberg D. Tissue sites of degradation of native and reductively methylated [14C]sucrose-labeled low density lipoprotein in rats. Contribution of receptor-dependent and receptor-independent pathways. J Biol Chem. 1982 Jul 25;257(14):8001–8008. [PubMed] [Google Scholar]
  4. Chao Y. S., Windler E. E., Chen G. C., Havel R. J. Hepatic catabolism of rat and human lipoproteins in rats treated with 17 alpha-ethinyl estradiol. J Biol Chem. 1979 Nov 25;254(22):11360–11366. [PubMed] [Google Scholar]
  5. Chin D. J., Gil G., Faust J. R., Goldstein J. L., Brown M. S., Luskey K. L. Sterols accelerate degradation of hamster 3-hydroxy-3-methylglutaryl coenzyme A reductase encoded by a constitutively expressed cDNA. Mol Cell Biol. 1985 Apr;5(4):634–641. doi: 10.1128/mcb.5.4.634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Daniel T. O., Schneider W. J., Goldstein J. L., Brown M. S. Visualization of lipoprotein receptors by ligand blotting. J Biol Chem. 1983 Apr 10;258(7):4606–4611. [PubMed] [Google Scholar]
  8. Eisenberg S. High density lipoprotein metabolism. J Lipid Res. 1984 Oct;25(10):1017–1058. [PubMed] [Google Scholar]
  9. Floren C. H., Kushwaha R. S., Hazzard W. R., Albers J. J. Estrogen-induced increase in uptake of cholesterol-rich very low density lipoproteins in perfused rabbit liver. Metabolism. 1981 Apr;30(4):367–375. doi: 10.1016/0026-0495(81)90117-7. [DOI] [PubMed] [Google Scholar]
  10. Goldstein J. L., Kita T., Brown M. S. Defective lipoprotein receptors and atherosclerosis. Lessons from an animal counterpart of familial hypercholesterolemia. N Engl J Med. 1983 Aug 4;309(5):288–296. doi: 10.1056/NEJM198308043090507. [DOI] [PubMed] [Google Scholar]
  11. Havel R. J., Kita T., Kotite L., Kane J. P., Hamilton R. L., Goldstein J. L., Brown M. S. Concentration and composition of lipoproteins in blood plasma of the WHHL rabbit. An animal model of human familial hypercholesterolemia. Arteriosclerosis. 1982 Nov-Dec;2(6):467–474. doi: 10.1161/01.atv.2.6.467. [DOI] [PubMed] [Google Scholar]
  12. Hay R. V., Pottenger L. A., Reingold A. L., Getz G. S., Wissler R. W. Degradation of I 125 -labelled serum low density lipoprotein in normal and estrogen-treated male rats. Biochem Biophys Res Commun. 1971 Sep 17;44(6):1471–1477. doi: 10.1016/s0006-291x(71)80251-6. [DOI] [PubMed] [Google Scholar]
  13. Kita T., Brown M. S., Bilheimer D. W., Goldstein J. L. Delayed clearance of very low density and intermediate density lipoproteins with enhanced conversion to low density lipoprotein in WHHL rabbits. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5693–5697. doi: 10.1073/pnas.79.18.5693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kovanen P. T., Bilheimer D. W., Goldstein J. L., Jaramillo J. J., Brown M. S. Regulatory role for hepatic low density lipoprotein receptors in vivo in the dog. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1194–1198. doi: 10.1073/pnas.78.2.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kovanen P. T., Brown M. S., Basu S. K., Bilheimer D. W., Goldstein J. L. Saturation and suppression of hepatic lipoprotein receptors: a mechanism for the hypercholesterolemia of cholesterol-fed rabbits. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1396–1400. doi: 10.1073/pnas.78.3.1396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kovanen P. T., Brown M. S., Goldstein J. L. Increased binding of low density lipoprotein to liver membranes from rats treated with 17 alpha-ethinyl estradiol. J Biol Chem. 1979 Nov 25;254(22):11367–11373. [PubMed] [Google Scholar]
  17. Kushwaha R. S., Hazzard W. R. Effect of exogenous estrogens on catabolism of VLDL in cholesterol-fed rabbits. Am J Physiol. 1981 Nov;241(5):E372–E377. doi: 10.1152/ajpendo.1981.241.5.E372. [DOI] [PubMed] [Google Scholar]
  18. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  19. Mahley R. W., Hui D. Y., Innerarity T. L., Weisgraber K. H. Two independent lipoprotein receptors on hepatic membranes of dog, swine, and man. Apo-B,E and apo-E receptors. J Clin Invest. 1981 Nov;68(5):1197–1206. doi: 10.1172/JCI110365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mahley R. W., Innerarity T. L. Lipoprotein receptors and cholesterol homeostasis. Biochim Biophys Acta. 1983 May 24;737(2):197–222. doi: 10.1016/0304-4157(83)90001-1. [DOI] [PubMed] [Google Scholar]
  21. Newman T. C., Dawson P. A., Rudel L. L., Williams D. L. Quantitation of apolipoprotein E mRNA in the liver and peripheral tissues of nonhuman primates. J Biol Chem. 1985 Feb 25;260(4):2452–2457. [PubMed] [Google Scholar]
  22. Pittman R. C., Carew T. E., Attie A. D., Witztum J. L., Watanabe Y., Steinberg D. Receptor-dependent and receptor-independent degradation of low density lipoprotein in normal rabbits and in receptor-deficient mutant rabbits. J Biol Chem. 1982 Jul 25;257(14):7994–8000. [PubMed] [Google Scholar]
  23. Russell D. W., Yamamoto T., Schneider W. J., Slaughter C. J., Brown M. S., Goldstein J. L. cDNA cloning of the bovine low density lipoprotein receptor: feedback regulation of a receptor mRNA. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7501–7505. doi: 10.1073/pnas.80.24.7501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Spady D. K., Bilheimer D. W., Dietschy J. M. Rates of receptor-dependent and -independent low density lipoprotein uptake in the hamster. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3499–3503. doi: 10.1073/pnas.80.11.3499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Spady D. K., Dietschy J. M. Dietary saturated triacylglycerols suppress hepatic low density lipoprotein receptor activity in the hamster. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4526–4530. doi: 10.1073/pnas.82.13.4526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stoudemire J. B., Renaud G., Shames D. M., Havel R. J. Impaired receptor-mediated catabolism of low density lipoproteins in fasted rabbits. J Lipid Res. 1984 Jan;25(1):33–39. [PubMed] [Google Scholar]
  27. Yamamoto T., Davis C. G., Brown M. S., Schneider W. J., Casey M. L., Goldstein J. L., Russell D. W. The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell. 1984 Nov;39(1):27–38. doi: 10.1016/0092-8674(84)90188-0. [DOI] [PubMed] [Google Scholar]

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