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de Bari O, Wang HH, Portincasa P, et al. The deletion of the estrogen receptor α gene reduces susceptibility to estrogen-induced cholesterol cholelithiasis in female mice. Biochim Biophys Acta. 2015;1852(10):2161-9doi: 10.1016/j.bbadis.2015.07.020.
de Bari, O., Wang, H. H., Portincasa, P., Liu, M., & Wang, D. Q. (2015). The deletion of the estrogen receptor α gene reduces susceptibility to estrogen-induced cholesterol cholelithiasis in female mice. Biochimica et biophysica acta, 1852(10), 2161-9. https://doi.org/10.1016/j.bbadis.2015.07.020
de Bari, Ornella, et al. "The deletion of the estrogen receptor α gene reduces susceptibility to estrogen-induced cholesterol cholelithiasis in female mice." Biochimica et biophysica acta vol. 1852,10 (2015): 2161-9. doi: https://doi.org/10.1016/j.bbadis.2015.07.020
de Bari O, Wang HH, Portincasa P, Liu M, Wang DQ. The deletion of the estrogen receptor α gene reduces susceptibility to estrogen-induced cholesterol cholelithiasis in female mice. Biochim Biophys Acta. 2015 Oct;1852(10):2161-9. doi: 10.1016/j.bbadis.2015.07.020. Epub 2015 Jul 30. PMID: 26232687; PMCID: PMC4701041.
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Biochim Biophys Acta. 2015 Oct;1852(10):2161-9. doi: 10.1016/j.bbadis.2015.07.020. Epub 2015 Jul 30.

The deletion of the estrogen receptor α gene reduces susceptibility to estrogen-induced cholesterol cholelithiasis in female mice.

Biochimica et biophysica acta

Ornella de Bari, Helen H Wang, Piero Portincasa, Min Liu, David Q-H Wang

Affiliations

  1. Department of Internal Medicine, Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
  2. Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
  3. Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
  4. Department of Internal Medicine, Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA. Electronic address: [email protected].

PMID: 26232687 PMCID: PMC4701041 DOI: 10.1016/j.bbadis.2015.07.020

Abstract

Compelling evidence has demonstrated that estrogen is a critical risk factor for gallstone formation and enhances cholesterol cholelithogenesis through the hepatic estrogen receptor α (ERα), but not ERβ. To study the lithogenic mechanisms of estrogen through ERα, we investigated whether the deletion of Erα protects against gallstone formation in ovariectomized (OVX) female mice fed a lithogenic diet and treated with 17β-estradiol (E2) at 0 or 6μg/day for 56days. Our results showed that the prevalence of gallstones was reduced from 100% in OVX ERα (+/+) mice to 30% in OVX ERα (-/-) mice in response to high doses of E2 and the lithogenic diet for 56days. Hepatic cholesterol secretion was significantly diminished in OVX ERα (-/-) mice compared to OVX ERα (+/+) mice even fed the lithogenic diet and treated with E2 for 56days. These alterations decreased bile lithogenicity by reducing cholesterol saturation index of gallbladder bile. Immunohistochemical studies revealed that ERα was expressed mainly in the gallbladder smooth muscle cells. High levels of E2 impaired gallbladder emptying function mostly through the ERα and cholecystokinin-1 receptor pathway, leading to gallbladder stasis in OVX ERα (+/+) mice. By contrast, gallbladder emptying function was greatly improved in OVX ERα (-/-) mice. This markedly retarded cholesterol crystallization and the growth and agglomeration of solid cholesterol crystals into microlithiasis and stones. In conclusion, the deletion of Erα reduces susceptibility to the formation of E2-induced gallstones by diminishing hepatic cholesterol secretion, desaturating gallbladder bile, and improving gallbladder contraction function in female mice.

Copyright © 2015 Elsevier B.V. All rights reserved.

Keywords: Bile flow; Bile salts; Biliary secretion; Cholesterol crystallization; Gallbladder motility; Lith gene

References

  1. Gastroenterology. 2004 Jul;127(1):239-49 - PubMed
  2. J Lipid Res. 1980 Feb;21(2):259-61 - PubMed
  3. N Engl J Med. 1976 Jan 22;294(4):189-92 - PubMed
  4. J Lipid Res. 1978 Sep;19(7):924-8 - PubMed
  5. J Lipid Res. 1978 Nov;19(8):945-55 - PubMed
  6. Metabolism. 1980 Jan;29(1):18-22 - PubMed
  7. N Engl J Med. 1980 Feb 14;302(7):362-4 - PubMed
  8. J Lipid Res. 1989 May;30(5):719-30 - PubMed
  9. J Reprod Med. 1980 Oct;25(4):187-90 - PubMed
  10. Gastroenterology. 1982 Apr;82(4):711-9 - PubMed
  11. N Engl J Med. 1989 Aug 31;321(9):563-9 - PubMed
  12. Gastroenterology. 1978 Jul;75(1):76-9 - PubMed
  13. J Clin Invest. 1991 Jan;87(1):237-46 - PubMed
  14. Gastroenterol Clin North Am. 1991 Mar;20(1):1-19 - PubMed
  15. Am J Epidemiol. 1991 Jul 15;134(2):186-95 - PubMed
  16. Gastroenterology. 1992 Nov;103(5):1657-63 - PubMed
  17. Hepatology. 1993 Jan;17(1):159-61 - PubMed
  18. Ann Intern Med. 1993 Jul 15;119(2):116-20 - PubMed
  19. Am J Public Health. 1993 Aug;83(8):1113-20 - PubMed
  20. Obstet Gynecol. 1994 Jan;83(1):5-11 - PubMed
  21. J Lipid Res. 1996 Mar;37(3):606-30 - PubMed
  22. J Lipid Res. 1997 Jul;38(7):1395-411 - PubMed
  23. Am J Physiol. 1998 Feb;274(2 Pt 1):G283-9 - PubMed
  24. Scand J Gastroenterol. 1998 Sep;33(9):993-7 - PubMed
  25. Gastroenterology. 1999 Sep;117(3):632-9 - PubMed
  26. J Biol Chem. 1959 Mar;234(3):466-8 - PubMed
  27. Res Nurs Health. 2004 Dec;27(6):382-91 - PubMed
  28. JAMA. 2005 Jan 19;293(3):330-9 - PubMed
  29. Mamm Genome. 2005 Mar;16(3):152-63 - PubMed
  30. Am J Physiol Gastrointest Liver Physiol. 2006 Feb;290(2):G269-76 - PubMed
  31. J Lipid Res. 2006 Apr;47(4):778-86 - PubMed
  32. Gastroenterology. 2006 Dec;131(6):1943-70 - PubMed
  33. Clin Chim Acta. 2007 Sep;384(1-2):80-5 - PubMed
  34. Hepatology. 2007 Sep;46(3):793-801 - PubMed
  35. Front Biosci. 2008;13:401-23 - PubMed
  36. Hepatology. 2008 Jun;47(6):2112-26 - PubMed
  37. Nutr Rev. 2008 Jun;66(6):343-8 - PubMed
  38. Br J Surg. 2008 Aug;95(8):1005-11 - PubMed
  39. Biochim Biophys Acta. 2009 Nov;1791(11):1037-47 - PubMed
  40. Biochim Biophys Acta. 2010 Feb;1801(2):138-46 - PubMed
  41. Gastroenterol Clin North Am. 2010 Jun;39(2):185-207, vii-viii - PubMed
  42. J Intern Med. 2010 Sep;268(3):279-85 - PubMed
  43. Hepatology. 2013 Jun;57(6):2407-17 - PubMed
  44. Ann Hepatol. 2014 Nov-Dec;13(6):728-45 - PubMed
  45. J Lipid Res. 1999 Nov;40(11):2066-79 - PubMed
  46. Gastroenterology. 2003 Sep;125(3):868-81 - PubMed
  47. J Lab Clin Med. 1982 Jun;99(6):798-805 - PubMed
  48. J Hepatol. 1987 Jun;4(3):318-26 - PubMed
  49. J Lipid Res. 1987 May;28(5):589-95 - PubMed
  50. J Lipid Res. 1987 Jul;28(7):828-39 - PubMed
  51. Hepatology. 1987 Sep-Oct;7(5):913-7 - PubMed
  52. Hepatology. 1988 Jul-Aug;8(4):907-13 - PubMed
  53. J Clin Invest. 1989 Sep;84(3):811-6 - PubMed
  54. Ann Surg. 1973 Oct;178(4):514-24 - PubMed

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