Research Status of Female Hormone in Cholesterol Gallstones_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

NIE Yungui , DING Youming , WANG Bin

Department of Hepatobiliary and Laparoscopic Surgery， Renmin Hospital of Wuhan University， Wuhan 430060， Hubei Province， China;

Corresponding author：

Keywords：

Estrogen; Progesterone; Cholesterol gallstone

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Objective 　To review the mechanisms of cholesterol gallstones caused by female hormone so as to explore new treatments to prevent gallstones associated with estrogen and progesterone.
Methods 　The literatures on gallstones related with female hormone were reviewed and the mechanisms of cholesterol gallstones were summarized.
Results 　The cholesterol gallstones mechanisms was affected by estrogen through genomic effects，and the nucleation of cholesterol was promoted by estrogen through nongenomic，which resulted in the formation of cholesterol gallstones. And the bile empty dysfunction associated with estrogen through nongenomic effects was also the reason of cholesterol gallstone formation. The G proteins α subunit responsible for the motility of gallbladder were disrupted by progesterone through genomic effects，and the ionic channels and signal transduction were also interfered through nongenomic pathway，which impaired the contraction of gallbladder. However，the nongenomic effects might not play an important role in the gallstones formation caused by progesterone.
Conclusions 　The mechanisms of cholesterol gallstones formation associated with female hormone are complicated，the understanding of chelesterol gallstones formation mechanisms might be helpful to prevent gallstones associated with estrogen and progesterone.

Citation： NIE Yungui,DING Youming,WANG Bin,.. Research Status of Female Hormone in Cholesterol Gallstones. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(8): 904-910. doi: Copy

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7.	Wang HH， Afdhal NH， Wang DQ. Overexpression of estrogen receptor alpha increases hepatic cholesterogenesis， leading to biliary hypersecretion in mice[J]. J Lipid Res， 2006， 47(4)：778-786.
8.	Ohashi A， Wang DQ. 17β-estradiol increases cholesterol cholelithogenesis in gallstone-resistant mice through mediating the expression of hepatic lipid transporters (Abstract)[J]. Gastroenterology， 2002， 122：A7.
9.	Wang HH， Afdhal NH， Wang DQ. The blockade of estrogen action by fulvestrant (ICI 182， 780) prevents cholesterol gallstone formation in the mouse (abstr)[J]. Hepatology， 2003， 38(4)：195A.
10.	Everson GT， McKinley C， Kern F Jr. Mechanisms of gallstone formation in women. Effects of exogenous estrogen (Premarin) and dietary cholesterol on hepatic lipid metabolism[J]. J Clin Invest， 1991， 87(1)：237-246.
11.	Coyne MJ， Bonorris GG， Chung A， et al. Estrogen enhances dietary cholesterol induction of saturated bile in the hamster[J]. Gastroenterology， 1978， 75(1)：76-79.
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13.	Yu L， Li-Hawkins J， Hammer RE， et al. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol[J]. J Clin Invest， 2002， 110(5)：671-680.
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1. Novacek G. Gender and gallstone disease[J]. Wien Med Wochenschr， 2006， 156(19-20)：527-533.
2. Bolukbas FF， Bolukbas C， Horoz M， et al. Risk factors associated with gallstone and biliary sludge formation during pregnancy[J]. J Gastroenterol Hepatol， 2006， 21(7)：1150-1153.
3. Shaffer EA. Gallstone disease：Epidemiology of gallbladder stone disease[J]. Best Pract Res Clin Gastroenterol， 2006， 20(6)：981-996.
4. Wang DQ， Afdhal NH. Genetic analysis of cholesterol gallstone formation：searching for Lith (gallstone) genes[J]. Curr Gastroenterol Rep， 2004， 6(2)：140-150.
5. Uhler ML，Marks JW， Voigt BJ， et al. Comparison of the impact of transdermal versus oral estrogens on biliary markers of gallstone formation in postmenopausal women[J]. J Clin Endocrinol Metab， 1998， 83(2)：410-414.
6. Wang HH， Afdhal NH， Wang DQ. Estrogen receptor alpha， but not beta， plays a major role in 17beta-estradiol-induced murine cholesterol gallstones[J]. Gastroenterology， 2004， 127(1)：239-249.
7. Wang HH， Afdhal NH， Wang DQ. Overexpression of estrogen receptor alpha increases hepatic cholesterogenesis， leading to biliary hypersecretion in mice[J]. J Lipid Res， 2006， 47(4)：778-786.
8. Ohashi A， Wang DQ. 17β-estradiol increases cholesterol cholelithogenesis in gallstone-resistant mice through mediating the expression of hepatic lipid transporters (Abstract)[J]. Gastroenterology， 2002， 122：A7.
9. Wang HH， Afdhal NH， Wang DQ. The blockade of estrogen action by fulvestrant (ICI 182， 780) prevents cholesterol gallstone formation in the mouse (abstr)[J]. Hepatology， 2003， 38(4)：195A.
10. Everson GT， McKinley C， Kern F Jr. Mechanisms of gallstone formation in women. Effects of exogenous estrogen (Premarin) and dietary cholesterol on hepatic lipid metabolism[J]. J Clin Invest， 1991， 87(1)：237-246.
11. Coyne MJ， Bonorris GG， Chung A， et al. Estrogen enhances dietary cholesterol induction of saturated bile in the hamster[J]. Gastroenterology， 1978， 75(1)：76-79.
12. Kuiper GG， Carlsson B， Grandien K， et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta[J]. Endocrinology， 1997， 138(3)：863-870.
13. Yu L， Li-Hawkins J， Hammer RE， et al. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol[J]. J Clin Invest， 2002， 110(5)：671-680.
14. Repa JJ， Berge KE， Pomajzl C， et al. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta[J]. J Biol Chem，2002， 277(21)：18793-18800.
15. Yu L， York J， von Bergmann K， et al. Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8[J]. J Biol Chem， 2003， 278(18)：15565-15570.
16. Jiang ZY， Parini P， Eggertsen G， et al. Increased expression of LXR alpha， ABCG5， ABCG8， and SR-BI in the liver from normolipidemic， nonobese Chinese gallstone patients[J]. J Lipid Res， 2008， 49(2)：464-472.
17. Cui W， Jiang ZY， Cai Q， et al. Decreased NPC1L1 expression in the liver from Chinese female gallstone patients[J]. Lipids Health Dis， 2010， 9：17.
18. Baskaran V， Vij U， Sahni P， et al. Do the progesterone receptors have a role to play in gallbladder cancer?[J]. Int J Gastrointest Cancer， 2005， 35(1)：61-68.
19. Temel RE， Tang W， Ma Y， et al. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a targetof ezetimibe[J]. J Clin Invest， 2007， 117(7)：1968-1978.
20. Altmann SW， Davis HR Jr， Zhu LJ， et al. Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption[J]. Science， 2004， 303(5661)：1201-1204.
21. Davis HR Jr， Zhu LJ， Hoos LM， et al. Niemann-Pick C1 like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis[J]. J Biol Chem， 2004， 279(32)：33586-33592.
22. Davies JP， Scott C， Oishi K， et al. Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia[J]. J Biol Chem， 2005， 280(13)：12710-12720.
23. Sané AT， Sinnett D， Delvin E， et al. Localization and role of NPC1L1 in cholesterol absorption in human intestine[J]. JLipid Res， 2006， 47(10)：2112-2120.
24. Eberlé D， Hegarty B， Bossard P， et al. SREBP transcription factors：master regulators of lipid homeostasis[J]. Biochimie， 2004， 86(11)：839-848.
25. Brown MS， Goldstein JL. The SREBP pathway：regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor[J]. Cell， 1997， 89(3)：331-340.
26. Horton JD， Goldstein JL， Brown MS. SREBPs：activators of the complete program of cholesterol and fatty acid synthesis in the liver[J]. J Clin Invest， 2002， 109(9)：1125-1131.
27. Goldstein JL， Brown MS. Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia[J]. J Biol Chem， 1974， 249(16)：5153-5162.
28. Brown MS， Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis[J]. Science， 1986， 232(4746)：34-47.
29. Duan LP， Wang HH， Ohashi A， et al. Role of intestinal sterol transporters Abcg5， Abcg8， and Npc1l1 in cholesterol absorption in mice：gender and age effects[J]. Am J Physiol Gastrointest Liver Physiol， 2006， 290(2)：G269-G276.
30. Plösch T， Bloks VW， Terasawa Y， et al. Sitosterolemia in ABC-transporter G5-deficient mice is aggravated on activation of the liver-X receptor[J]. Gastroenterology， 2004， 126(1)：290-300.
31. Wang HH， Patel SB， Carey MC， et al. Increased cholesterol and sitostanol absorption and reduced biliary cholesterol secretion in ATP-binding cassette transporter Abcg8 (-/-) mice[J]. Gastroenterology， 2005， 128：A678.
32. Yu L， Hammer RE， Li-Hawkins J， et al. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion[J]. Proc Natl Acad Sci USA， 2002， 99(25)：16237-16242.
33. Duan LP， Wang HH， Wang DQ. Cholesterol absorption is mainly regulated by the jejunal and ileal ATP-binding cassette sterol efflux transporters Abcg5 and Abcg8 in mice[J]. J Lipid Res， 2004， 45(7)：1312-1323.
34. Wang DQ， Tazuma S， Cohen DE， et al. Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption：studies in the gallstone-susceptible mouse[J]. Am J Physiol Gastrointest Liver Physiol， 2003， 285(3)：G494-G502.
35. Brown AC， Wrenn SP， Suresh N， et al. Gender differences in cholesterol nucleation in native bile：estrogen is a potential contributory factor[J]. J Membr Biol， 2009， 232(1-3)：35-45.
36. George KS， Wu S. Lipid raft：A floating island of death or survival[J]. Toxicol Appl Pharmacol， 2012， 259(3)：311-319.
37. Pani B， Singh BB. Lipid rafts/caveolae as microdomains of calcium signaling[J]. Cell calcium， 2009， 45(6)：625-633.
38. Whiting KP， Restall CJ， Brain PF. Steroid hormone-induced effects on membrane fluidity and their potential roles in non-genomic mechanisms[J]. Life Sci， 2000， 67(7)：743-757.
39. Filardo EJ， Quinn JA， Sabo E. Association of the membrane estrogen receptor， GPR30， with breast tumor metastasis and transactivation of the epidermal growth factor receptor[J]. Steroids， 2008， 73(9-10)：870-873.
40. Filardo EJ， Thomas P. GPR30：a seven-transmembrane-spanning estrogen receptor that triggers EGF release[J]. Trends Endocrinol Metab， 2005， 16(8)：362-367.
41. Tierney S， Qian Z， Burrow C， et al. Estrogen inhibits sphincter of Oddi motility[J]. J Surg Res， 1994， 57(1)：69-73.
42. Kiaii B， Xu QW， Shaffer EA. The basis for progesterone impairment of gallbladder contractility in male Guinea pigs in vitro[J]. J Surg Res， 1998， 79(2)：97-102.
43. Chen Q， Chitinavis V， Xiao Z， et al. Impaired G protein function in gallbladder muscle from progesterone-treated Guinea pigs[J]. Am J Physiol， 1998， 274(2 pt 1)：G283-G289.
44. Cong P， Pricolo V， Biancani P， et al. High levels of caveolar cholesterol inhibit progesterone-induced genomic actions in human and Guinea pig gallbladder muscle[J]. Am J Physiol Gastrointest Liver Physiol， 2009， 296(4)：G948-G954.
45. Tierney S， Nakeeb A， Wong O， et al. Progesterone alters biliary flow dynamics[J]. Ann Surg， 1999， 229(2)：205-209.
46. Xiao ZL， Biancani P， Behar J. Effects of progesterone on motility and prostaglandin levels in the distal Guinea pig colon[J]. Am J Physiol Gastrointest Liver Physiol， 2009， 297(5)：G886-G893.
47. Chen Q， Xiao ZL， Biancani P， et al. Downregulation of galphaq-11 protein expression in Guinea pig antral and colonic circular muscle during pregnancy[J]. Am J Physiol， 1999， 276(4 Pt 1)：G895-G900.
48. Xiao ZL， Chen Q， Biancani P， et al. Mechanisms of gallbladder hypomotility in pregnant Guinea pigs[J]. Gastroenterology， 1999， 116(2)：411-419.
49. Cheng L， Pricolo V， Biancani P， et al. Overexpression of progesterone receptor B increases sensitivity of human colon muscle cells to progesterone[J]. Am J Physiol Gastrointest Liver Physiol， 2008， 295(3)：G493-G502.
50. Cheng L， Biancani P， Behar J. Progesterone receptor A mediates VIP inhibition of contraction[J]. Am J Physiol Gastrointest Liver Physiol， 2010， 298(3)：G433-G439.
51. Cong P， Xiao ZL， Biancani P， et al. Prostaglandins mediate tonic contraction of the Guinea pig and human gallbladder[J]. Am J Physiol Gastrointest Liver Physiol， 2007， 292(1)：G409-G418.
52. Xiao ZL， Cao W， Biancani P， et al. Nongenomic effects of progesterone on the contraction of muscle cells from the Guinea pig colon[J]. Am J Physiol Gastrointest Liver Physiol， 2006， 290(5)：G1008-G1015.
53. Zhang L， Bonev AD， Nelson MT， et al. Ionic basis of the action potential of Guinea pig gallbladder smooth muscle cells[J]. Am J Physiol， 1993， 265(6 pt 1)：C1552-C1561.
54. Jennings LJ， Xu QW， Firth TA， et al. Cholesterol inhibits spontaneous action potentials and calcium currents in Guinea pig gallbladder smooth muscle[J]. Am J Physiol， 1999， 277(5 pt 1)：G1017-G1026.
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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research Status of Female Hormone in Cholesterol Gallstones

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