Liver X receptor (LXR) and the reproductive system - A potential novel target for therapeutic intervention

Pharmacological Reports

Volumn 62, Issue 1, 2010, Pages 15-27

  Bełtowski, Jerzy ^a   Semczuk, Andrzej ^a  

^a MEDICAL UNIVERSITY OF LUBLIN   (Poland)

Author keywords

Breast cancer; Infertility; Liver X receptor; Ovarian hyperstimulation syndrome; Oxysterols; Prostate cancer

Indexed keywords

GONADOTROPIN; LIVER X RECEPTOR AGONIST; LIVER X RECEPTOR ALPHA; LIVER X RECEPTOR BETA;

AGING; CHOLESTEROL SYNTHESIS; DRUG TARGETING; FEMALE GENITAL SYSTEM; FEMALE INFERTILITY; GENE FUNCTION; GENE LOCATION; GENE STRUCTURE; GENE TARGETING; GENITAL SYSTEM; HOMEOSTASIS; INSULIN RESISTANCE; KNOCKOUT MOUSE; LIGAND BINDING; MALE GENITAL SYSTEM; MALE INFERTILITY; MEIOSIS; NONHUMAN; OOCYTE; OVARY HYPERSTIMULATION; PLACENTA; REVIEW; SIGNAL TRANSDUCTION; TROPHOBLAST; UTERUS CONTRACTILITY;

EID: 77950845578     PISSN: 22995684     EISSN: 22995684     Source Type: Journal    
DOI: 10.1016/S1734-1140(10)70239-5     Document Type: Review

References (72)

1. Baranowski M: Biological role of liver X receptors. J Physiol Pharmacol, 2008, 59, Suppl 7, 31-55.
2. Bełtowski J: Liver X receptors (LXR) as therapeutic targets in dyslipidemia. Cardiovasc Ther, 2008, 26, 297-316.
3. Björkhem I: Rediscovery of cerebrosterol. Lipids, 2007, 42,5-14.
4. Bradley MN, Hong C, Chen M, Joseph SB, Wilpitz DC, Wang X, Lusis AJ et al.: Ligand activation of LXR reverses atherosclerosis and cellular cholesterol overload in mice lacking LXR and apoE. J Clin Invest, 2007, 117,2337-2346.
5. Byskov AG, Andersen CY, Nordholm L, Thøgersen H, Xia G, Wassmann O, Andersen JV et al.: Chemical structure of sterols that activate oocyte meiosis. Nature, 1995, 374,559-5562.
6. Byskov AG, Yding Andersen C, Hossaini A, Guoliang X: Cumulus cells of oocyte-cumulus complexes secrete a meiosis-activating substance when stimulated with FSH. Mol Reprod Dev, 1997, 46, 296-305.
7. Castrillo A, Joseph SB, Marathe C, Mangelsdorf DJ, Tontonoz P: Liver X receptor-dependent repression of matrix metalloproteinase-9 expression in macrophages. J Biol Chem, 2003, 278, 10443-10449.
8. Cavilla JL, Kennedy CR, Baltsen M, Klentzeris LD, Byskov AG, Hartshorne GM: The effects of meiosis activating sterol on in-vitro maturation and fertilization of human oocytes from stimulated and unstimulated ovaries. Hum Reprod, 2001, 16, 547-555.
9. Chen W, Chen G, Head DL, Mangelsdorf DJ, Russell DW: Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab, 2007, 5, 73-79.
10. Chuu CP, Hiipakka RA, Kokontis JM, Fukuchi J, Chen RY, Liao S: Inhibition of tumor growth and progression of LNCaP prostate cancer cells in athymic mice by androgen and liver X receptor agonist. Cancer Res, 2006, 66,6482-6486.
11. Cummins CL, Volle DH, Zhang Y, McDonald JG, Sion B, Lefrancois-Martinez AM, Caira F et al.: Liver X receptors regulate adrenal cholesterol balance. J Clin Invest, 2006, 116, 1902-1912.
12. Devoto L, Kohen P, Vega M, Castro O, González RR, Retamales I, Carvallo P et al.: Control of human luteal steroidogenesis. Mol Cell Endocrinol, 2002, 186, 137-141.
13. Drouineaud V, Sagot P, Garrido C, Logette E, Deckert V, Gambert P, Jimenez C et al.: Inhibition of progesterone production in human luteinized granulosa cells treated with LXR agonists. Mol Hum Reprod, 2007, 13, 373-379.
14. Duval C, Touche V, Tailleux A, Fruchart JC, Fievet C, Clavey V, Staels B, Lestavel S: Niemann-Pick C1 like 1 gene expression is down-regulated by LXR activators in the intestine. Biochem Biophys Res Commun, 2006, 340,1259-1263.
15. Edwards PA, Kennedy MA, Mak PA: LXRs; oxysterolactivated nuclear receptors that regulate genes controlling lipid homeostasis. Vascul Pharmacol, 2002, 38, 249-256.
16. Frenoux JM, Vernet P, Volle DH, Britan A, Saez F, Kocer A, Henry-Berger J et al.: Nuclear oxysterol receptors, LXRs, are involved in the maintenance of mouse caput epididymidis structure and functions. J Mol Endocrinol, 2004,33,361-375.
17. Fukuchi J, Kokontis JM, Hiipakka RA, Chuu CP, Liao S: Antiproliferative effect of liver X receptor agonists on LNCaP human prostate cancer cells. Cancer Res, 2004, 64,7686-7689.
18. Gabbi C, Warner M, Gustafsson JA: Minireview: liver X receptor: emerging roles in physiology and diseases. Mol Endocrinol, 2009, 23, 129-136.
19. Gong H, Guo P, Zhai Y, Zhou J, Uppal H, Jarzynka MJ, Song WC et al.: Estrogen deprivation and inhibition of breast cancer growth in vivo through activation of the orphan nuclear receptor liver X receptor. Mol Endocrinol, 2007,21,1781-1790.
20. Grøndahl C, Hansen TH, Marky-Nielsen K, Ottesen JL, Hyttel P: Human oocyte maturation in vitro is stimulated by meiosis-activating sterol. Hum Reprod, 2000, 15, Suppl 5, 3-10.
21. Grøndahl C, Lessl M, Faerge I, Hegele-Hartung C, Wassermann K, Ottesen JL: Meiosis-activating sterolmediated resumption of meiosis in mouse oocytes in vitro is influenced by protein synthesis inhibition and cholera toxin. Biol Reprod, 2000, 62, 775-780.
22. Henry-Berger J, Mouzat K, Baron S, Bernabeu C, Marceau G, Saru JP, Sapin V et al.: Endoglin (CD105) expression is regulated by the liver X receptor alpha (NR1H3) in human trophoblast cell line JAR. Biol Reprod, 2008, 78, 968-975.
23. Hong C, Tontonoz P: Coordination of inflammation and metabolism by PPAR and LXR nuclear receptors. Curr Opin Genet Dev, 2008, 18, 461-467.
24. http://www.clinicaltrials.gov; ClinicalTRials.gov/Identifier:NCT00366523.
25. Infante J, Rodríguez-Rodríguez E, Mateo I, Llorca J, Vázquez-Higuera JL, Berciano J, Combarros O: Genegene interaction between heme oxygenase-1 and liver X receptor-beta and Alzheimer's disease risk. Neurobiol Aging, 2010, 31, 710-714.
26. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ: An oxysterol signalling pathway mediated by the nuclear receptor LXR. Nature, 1996, 383, 728-731.
27. Janowski BA, Grogan MJ, Jones SA, Wisely GB, Kliewer SA, Corey EJ, Mangelsdorf DJ: Structural requirements of ligands for the oxysterol liver X receptors LXR and LXR. Proc Natl Acad Sci USA, 1999, 96, 266-271.
28. Kotokorpi P, Ellis E, Parini P, Nilsson LM, Strom S, Steffensen KR, Gustafsson JA, Mode A: Physiological differences between human and rat primary hepatocytes in response to liver X receptor activation by 3-[3-[N-(2-chloro-3-trifluoromethylbenzyl)-(2,2-diphenylethyl)-amino]propyloxy]phenylacetic acid hydrochloride (GW3965). Mol Pharmacol, 2007, 72, 947-955.
29. Kratzer A, Buchebner M, Pfeifer T, Becker TM, Uray G, Miyazaki M, Miyazaki-Anzai S et al.: Synthetic LXR agonist attenuates plaque formation in apoE-/-mice without inducing liver steatosis and hypertriglyceridemia. J Lipid Res, 2009, 50, 312-326.
30. Laffitte BA, Repa JJ, Joseph SB, Wilpitz DC, Kast HR, Mangelsdorf DJ, Tontonoz P: LXRs control lipidinducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proc Natl Acad Sci USA, 2001,98,507-512.
31. Lee JH, Gong H, Khadem S, Lu Y, Gao X, Li S, Zhang J, Xie W: Androgen deprivation by activating the liver X receptor. Endocrinology, 2008, 149, 3778-3788.
32. Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB, Su JL, Sundseth SS et al.: Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J Biol Chem, 1997, 272, 3137-3140.
33. Legry V, Cottel D, Ferrières J, Chinetti G, Deroide T, Staels B, Amouyel P, Meirhaeghe A: Association between liver X receptor gene polymorphisms and risk of metabolic syndrome in French populations. Int J Obes, 2008, 32, 421-428.
34. López-Novoa JM: Soluble endoglin is an accurate predictor and a pathogenic molecule in pre-eclampsia. Nephrol Dial Transplant, 2007, 22, 712-714.
35. Lundin K, Ziebe S, Bergh C, Loft A, Selleskog U, Nilsson L, Grøndahl C: Joan-Carles Arce for the CEMAS I Study Group: Effect of rescuing donated immature human oocytes derived after FSH/hCG stimulation following in vitro culture with or without Follicular Fluid Meiosis Activating Sterol (FF-MAS) -an embryo chromosomal and morphological analysis. J Assist Reprod Genet, 2007, 24, 87-90.
36. Mak PA, Laffitte BA, Desrumaux C, Joseph SB, Curtiss LK, Mangelsdorf DJ, Tontonoz P, Edwards PA: Regulated expression of the apolipoprotein E/C-I/C-IV/C-II gene cluster in murine and human macrophages. A critical role for nuclear liver X receptors and.JBiol Chem, 2002, 277, 31900-31908.
37. Marceau G, Volle DH, Gallot D, Mangelsdorf DJ, Sapin V, Lobaccaro JM: Placental expression of the nuclear receptors for oxysterols LXR and LXR during mouse and human development. Anat Rec A Discov Mol Cell Evol Biol, 2005, 283, 175-181.
38. Marín Bivens CL, Lindenthal B, O'Brien MJ, Wiggles-worth K, Blume T, Grøndahl C, Eppig JJ: A synthetic analogue of meiosis-activating sterol (FF-MAS) is a potent agonist promoting meiotic maturation and preimplantation development of mouse oocytes maturing in vitro. Hum Reprod, 2004, 19, 2340-2344.
39. Mascrez B, Ghyselinck NB, Watanabe M, Annicotte JS, Chambon P, Auwerx J, Mark M: Ligand-dependent contribution of RXR to cholesterol homeostasis in Sertoli cells. EMBO Rep, 2004, 5, 285-290.
40. Menke JG, Macnaul KL, Hayes NS, Baffic J, Chao YS, Elbrecht A, Kelly LJ et al.: A novel liver X receptor agonist establishes species differences in the regulation of cholesterol 7 -hydroxylase (CYP7a). Endocrinology, 2002,143,2548-2558.
41. Mouzat K, Prod'Homme M, Volle DH, Sion B, Dechelotte P, Gauthier K, Vanacker JM, Lobaccaro JM: Oxysterol nuclear receptor LXR regulates cholesterol homeostasis and contractile function in mouse uterus. J Biol Chem, 2007, 282, 4693-4701.
42. Mouzat K, Volat F, Baron S, Alves G, Pommier AJ, Volle DH, Marceau G et al.: Absence of nuclear receptors for oxysterols Liver X Receptor (LXR) induces ovarian hyperstimulation syndrome in mice. Endocrinology, 2009, 150, 3369-3375.
43. Nilsson M, Stulnig TM, Lin CY, Yeo AL, Nowotny P, Liu ET, Steffensen KR: Liver X receptors regulate adrenal steroidogenesis and hypothalamic-pituitary-adrenal feedback. Mol Endocrinol, 2007, 21, 126-137.
44. Papadopoulos V: Cholesterol homeostasis and infertility: the liver X receptor connection. Endocrinology, 2005, 146,2517-2518.
45. Papassotiropoulos A, Lutjohann D, Bagli M, Locatelli S, Jessen F, Rao ML, Maier W et al.: Plasma 24S-hydroxy-cholesterol: a peripheral indicator of neuronal degeneration and potential state marker for Alzheimer's disease. Neuroreport, 2000, 11, 1959-1962.
46. Pavan L, Hermouet A, Tsatsaris V, Therond P, Sawamura T, Evain-Brion D, Fournier T: Lipids from oxidized low-density lipoprotein modulate human trophoblast invasion: involvement of nuclear liver X receptors. Endocrinology, 2004, 145, 4583-4591.
47. Peet DJ, Turley SD, Ma W, Janowski BA, Lobaccaro JM, Hammer RE, Mangelsdorf DJ: Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR. Cell, 1998, 93, 693-704.
48. Pikuleva IA: Cholesterol-metabolizing cytochromes P450. Drug Metab Dispos, 2006, 34, 513-20.
49. Pikuleva IA: Cytochrome P450s and cholesterol homeostasis. Pharmacol Ther, 2006, 112, 761-773.
50. Plösch T, van Straten EM, Kuipers F: Cholesterol transport by the placenta: placental liver X receptor activity as a modulator of fetal cholesterol metabolism? Placenta, 2007,28,604-610.
51. Repa JJ, Berge KE, Pomajzl C, Richardson JA, Hobbs H, Mangelsdorf DJ: Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors and.JBiolChem,2002,277,18793-18800.
52. Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B et al.: Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXR and LXR. Genes Dev, 2000,14,2819-2830.
53. Rigamonti E, Helin L, Lestavel S, Mutka AL, Lepore M, Fontaine C, Bouhlel MA et al.: Liver X receptor activation controls intracellular cholesterol trafficking and esterification in human macrophages. Circ Res, 2005, 97, 682-689.
54. Robertson KM, Schuster GU, Steffensen KR, Hovatta O, Meaney S, Hultenby K, Johansson LC et al.: The liver X receptoris essential for maintaining cholesterol homeo-stasis in the testis. Endocrinology, 2005, 146, 2519-2530.
55. Saez F, Chabory E, Cadet R, Vernet P, Baron S, Lobaccaro JM, Drevet JR: Liver X receptors and epididymal epithelium physiology. Asian J Androl, 2007, 9, 574-582.
56. Schroepfer GJ: Oxysterols: modulators of cholesterol metabolism and other processes. Physiol Rev, 2000, 80, 361-554.
57. Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, Li L, Schwendner S et al.: Role of LXRs in control of lipogenesis. Genes Dev, 2000, 14, 2831-2838.
58. Selva DM, Hirsch-Reinshagen V, Burgess B, Zhou S, Chan J, McIsaac S, Hayden MR et al.: The ATP-binding cassette transporter 1 mediates lipid efflux from Sertoli cells and influences male fertility. J Lipid Res, 2004, 45, 1040-1050.
59. Skilton MR: Intrauterine risk factors for precocious atherosclerosis. Pediatrics, 2008, 121, 570-574.
60. Smitz J, Picton HM, Platteau P, Rutherford A, Cortvrindt R, Clyde J, Nogueira D et al.: Principal findings from a multicenter trial investigating the safety of follicular-fluid meiosis-activating sterol for in vitro maturation of human cumulus-enclosed oocytes. Fertil Steril, 2007, 87, 949-964.
61. Steffensen KR, Robertson K, Gustafsson JA, Andersen CY: Reduced fertility and inability of oocytes to resume meiosis in mice deficient of the Lxr genes. Mol Cell Endocrinol, 2006, 256, 9-16.
62. Stefulj J, Panzenboeck U, Becker T, Hirschmugl B, Schweinzer C, Lang I, Marsche G et al.: Human endothelial cells of the placental barrier efficiently deliver cholesterol to the fetal circulation via ABCA1 and ABCG1. Circ Res, 2009, 104, 600-608.
63. Torra IP, Ismaili N, Feig JE, Xu CF, Cavasotto C, Pancratov R, Rogatsky I et al.: Phosphorylation of liver X receptor selectively regulates target gene expression in macrophages. Mol Cell Biol, 2008, 28, 2626-2636.
64. Volle DH, Mouzat K, Duggavathi R, Siddeek B, Dechelotte P, Sion B, Veyssiere G et al.: Multiple roles of the nuclear receptors for oxysterols liver X receptor to maintain male fertility. Mol Endocrinol, 2007, 21, 1014-1027.
65. Wang Y, Rogers PM, Su C, Varga G, Stayrook KR, Burris TP: Regulation of cholesterologenesis by the oxysterol receptor, LXR.JBiolChem,2008,283, 26332-26339.
66. Wassif CA, Yu J, Cui J, Porter FD, Javitt NB: 27-Hydroxylation of 7-and 8-dehydrocholesterol in Smith-Lemli-Opitz syndrome: a novel metabolic pathway. Steroids, 2003, 68, 497-502.
67. Weedon-Fekjaer MS, Duttaroy AK, Nebb HI: Liver X receptors mediate inhibition of hCG secretion in a human placental trophoblast cell line. Placenta, 2005, 26, 721-728.
68. Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, Mangelsdorf DJ: LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev, 1995, 9, 1033-1045.
69. Wong J, Quinn CM, Gelissen IC, Brown AJ: Endogenous 24(S),25-epoxycholesterol fine-tunes acute control of cellular cholesterol homeostasis. J Biol Chem, 2008, 283,700-707.
70. Woollett LA: Maternal cholesterol in fetal development: transport of cholesterol from the maternal to the fetal circulation. Am J Clin Nutr, 2005, 82, 1155-1161.
71. Yang C, McDonald JG, Patel A, Zhang Y, Umetani M, Xu F, Westover EJ et al.: Sterol intermediates from cho-lesterol biosynthetic pathway as liver X receptor ligands. J Biol Chem, 2006, 281, 27816-27826.
72. Yu L, York J, von Bergmann K, Lutjohann D, Cohen JC, Hobbs HH: Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette trans-porters G5 and G8. J Biol Chem, 2003, 278, 15565-15570.