The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Nr5a2  -  nuclear receptor subfamily 5, group A,...

Mus musculus

Synonyms: AU020803, D1Ertd308e, Ftf, LRH-1, Liver receptor homolog 1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Nr5a2


High impact information on Nr5a2

  • LRH-1 is an orphan nuclear receptor predominantly expressed in tissues of endodermal origin, where it controls development and cholesterol homeostasis [6].
  • Mutating the conserved arginine in helix 2 reduced LRH-1 receptor activity and coregulator recruitment, consistent with the partial loss-of-function phenotype exhibited by an analogous SF-1 human mutant [7].
  • Here, we report structural and biochemical analyses of the LRH-1/SHP interaction [8].
  • LRH-1 gene expression is reduced in tumors that express elevated levels of the proinflammatory cytokine TNF-alpha [2].
  • Reciprocally, decreased LRH-1 expression in Lrh-1+/- mice attenuates TNF-alpha expression [2].

Biological context of Nr5a2

  • FTF recognizes the DNA sequence 5'-TCAAGGTCA-3', the canonical recognition motif for FTZ-F1 receptors. cDNA sequence homologies indicate that rat FTF is the ortholog of mouse LRH-1 and Xenopus xFF1rA [9].
  • Amino acid substitutions revealed that Ad4BP/SF-1 and LRH-1 preferentially interact with L(+1)XXLL-related motifs containing serine, tyrosine, serine, and threonine at positions -2, +2, +3, and +6, respectively [10].
  • In this report, we use mutagenesis and reporter gene assays to carry out a detailed analysis on the hinge region and the proximal ligand binding domain (LBD) of human (h) LRH-1 that possess important regulatory functions [11].
  • These results indicate that induction of Mrp3 after BDL is due to Tnfalpha-dependent up-regulation of Lrh-1 [1].
  • The combined treatment of forskolin and phorbol ester (which mimic PGE2) as well as LRH-1, which maximally induced reporter gene expression (140-fold), was also completely inhibited by SHP [12].

Anatomical context of Nr5a2

  • In vitro and in vivo results show that LRH-1 plays an essential role in the maintenance of Oct4 expression in ES cells at the epiblast stage of embryonic development, thereby maintaining pluripotence at this crucial developmental stage prior to segregation of the primordial germ cell lineage at gastrulation [13].
  • LRH-1 protein was found in Caco-2 cells and mouse ileum, but not IEC-6 cells or rat ileum [14].
  • LRH-1 expression was first detected in the urogenital ridge before sexual determination, in primordial germ cells and surrounding somatic cells; expression persisted after differentiation into testes and ovaries [15].
  • Of interest, LRH-1 expression declined in the developing ovary and testis at embryonic day 15.5 but increased again just after birth in the ovary in granulosa cells and transiently in oocytes of developing follicles [15].
  • However, OR2.0 consists of 2945 bp, is expressed in the livers and the adrenal glands, and is considered to be the chicken counterpart of mouse LRH-1, which is a member of the FTZ-F1 family in mammals [16].

Associations of Nr5a2 with chemical compounds

  • Likewise, Lrh-1+/- mice are protected against the formation of aberrant crypt foci in the colon of mice exposed to the carcinogen azoxymethane [2].
  • In support of this hypothesis, we show that 9-cis-retinoic acid, acting through RXR, inhibits both the basal and PGC-1alpha-induced transcriptional activity of LRH-1 [17].
  • METHODS: Expression of LRH-1 mRNA in juvenile (30 days old) and adult (60 days old) mouse brain was examined using non-radioactive in situ hybridization with digoxigenin labeled cRNA probes and with RT PCR using specific primers [18].
  • LRH-1 expression was found to be abundant and highly restricted to cells involved in estrogen biosynthesis-granulosa cells during the estrous cycle, and in corpora lutea (CL) of pregnancy [19].
  • GATA factors and the nuclear receptors, steroidogenic factor 1/liver receptor homolog 1, are key mutual partners in the regulation of the human 3beta-hydroxysteroid dehydrogenase type 2 promoter [20].
  • LRH-1 deficiency in either tissue changed mRNA levels of genes involved in cholesterol and bile acid homeostasis [21].

Co-localisations of Nr5a2

  • LRH-1 is colocalized with Oct4 in the inner cell mass and the epiblast of embryos at early developmental stages [13].

Other interactions of Nr5a2


Analytical, diagnostic and therapeutic context of Nr5a2


  1. Tumor necrosis factor alpha-dependent up-regulation of Lrh-1 and Mrp3(Abcc3) reduces liver injury in obstructive cholestasis. Bohan, A., Chen, W.S., Denson, L.A., Held, M.A., Boyer, J.L. J. Biol. Chem. (2003) [Pubmed]
  2. Liver receptor homolog 1 contributes to intestinal tumor formation through effects on cell cycle and inflammation. Schoonjans, K., Dubuquoy, L., Mebis, J., Fayard, E., Wendling, O., Haby, C., Geboes, K., Auwerx, J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes. Clyne, C.D., Speed, C.J., Zhou, J., Simpson, E.R. J. Biol. Chem. (2002) [Pubmed]
  4. Liver receptor homolog 1 is a negative regulator of the hepatic acute-phase response. Venteclef, N., Smith, J.C., Goodwin, B., Delerive, P. Mol. Cell. Biol. (2006) [Pubmed]
  5. LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease. Coste, A., Dubuquoy, L., Barnouin, R., Annicotte, J.S., Magnier, B., Notti, M., Corazza, N., Antal, M.C., Metzger, D., Desreumaux, P., Brunner, T., Auwerx, J., Schoonjans, K. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  6. Synergy between LRH-1 and beta-catenin induces G1 cyclin-mediated cell proliferation. Botrugno, O.A., Fayard, E., Annicotte, J.S., Haby, C., Brennan, T., Wendling, O., Tanaka, T., Kodama, T., Thomas, W., Auwerx, J., Schoonjans, K. Mol. Cell (2004) [Pubmed]
  7. Structural basis for ligand-independent activation of the orphan nuclear receptor LRH-1. Sablin, E.P., Krylova, I.N., Fletterick, R.J., Ingraham, H.A. Mol. Cell (2003) [Pubmed]
  8. Structural and biochemical basis for selective repression of the orphan nuclear receptor liver receptor homolog 1 by small heterodimer partner. Li, Y., Choi, M., Suino, K., Kovach, A., Daugherty, J., Kliewer, S.A., Xu, H.E. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. The alpha1-fetoprotein locus is activated by a nuclear receptor of the Drosophila FTZ-F1 family. Galarneau, L., Paré, J.F., Allard, D., Hamel, D., Levesque, L., Tugwood, J.D., Green, S., Bélanger, L. Mol. Cell. Biol. (1996) [Pubmed]
  10. LXXLL-related motifs in Dax-1 have target specificity for the orphan nuclear receptors Ad4BP/SF-1 and LRH-1. Suzuki, T., Kasahara, M., Yoshioka, H., Morohashi, K., Umesono, K. Mol. Cell. Biol. (2003) [Pubmed]
  11. Molecular mechanism for the potentiation of the transcriptional activity of human liver receptor homolog 1 by steroid receptor coactivator-1. Xu, P.L., Liu, Y.Q., Shan, S.F., Kong, Y.Y., Zhou, Q., Li, M., Ding, J.P., Xie, Y.H., Wang, Y. Mol. Endocrinol. (2004) [Pubmed]
  12. Inhibition of aromatase transcription via promoter II by short heterodimer partner in human preadipocytes. Kovacic, A., Speed, C.J., Simpson, E.R., Clyne, C.D. Mol. Endocrinol. (2004) [Pubmed]
  13. Orphan nuclear receptor LRH-1 is required to maintain Oct4 expression at the epiblast stage of embryonic development. Gu, P., Goodwin, B., Chung, A.C., Xu, X., Wheeler, D.A., Price, R.R., Galardi, C., Peng, L., Latour, A.M., Koller, B.H., Gossen, J., Kliewer, S.A., Cooney, A.J. Mol. Cell. Biol. (2005) [Pubmed]
  14. Liver receptor homologue-1 mediates species- and cell line-specific bile acid-dependent negative feedback regulation of the apical sodium-dependent bile acid transporter. Chen, F., Ma, L., Dawson, P.A., Sinal, C.J., Sehayek, E., Gonzalez, F.J., Breslow, J., Ananthanarayanan, M., Shneider, B.L. J. Biol. Chem. (2003) [Pubmed]
  15. Temporal and spatial expression of liver receptor homologue-1 (LRH-1) during embryogenesis suggests a potential role in gonadal development. Hinshelwood, M.M., Shelton, J.M., Richardson, J.A., Mendelson, C.R. Dev. Dyn. (2005) [Pubmed]
  16. Molecular cloning of chicken FTZ-F1-related orphan receptors. Kudo, T., Sutou, S. Gene (1997) [Pubmed]
  17. Coactivation of liver receptor homologue-1 by peroxisome proliferator-activated receptor gamma coactivator-1alpha on aromatase promoter II and its inhibition by activated retinoid X receptor suggest a novel target for breast-specific antiestrogen therapy. Safi, R., Kovacic, A., Gaillard, S., Murata, Y., Simpson, E.R., McDonnell, D.P., Clyne, C.D. Cancer Res. (2005) [Pubmed]
  18. Widespread expression of liver receptor homolog 1 in mouse brain. Grgurevic, N., Tobet, S., Majdic, G. Neuro Endocrinol. Lett. (2005) [Pubmed]
  19. Expression of LRH-1 and SF-1 in the mouse ovary: localization in different cell types correlates with differing function. Hinshelwood, M.M., Repa, J.J., Shelton, J.M., Richardson, J.A., Mangelsdorf, D.J., Mendelson, C.R. Mol. Cell. Endocrinol. (2003) [Pubmed]
  20. GATA factors and the nuclear receptors, steroidogenic factor 1/liver receptor homolog 1, are key mutual partners in the regulation of the human 3beta-hydroxysteroid dehydrogenase type 2 promoter. Martin, L.J., Taniguchi, H., Robert, N.M., Simard, J., Tremblay, J.J., Viger, R.S. Mol. Endocrinol. (2005) [Pubmed]
  21. Liver receptor homolog-1 regulates bile acid homeostasis but is not essential for feedback regulation of bile acid synthesis. Lee, Y.K., Schmidt, D.R., Cummins, C.L., Choi, M., Peng, L., Zhang, Y., Goodwin, B., Hammer, R.E., Mangelsdorf, D.J., Kliewer, S.A. Mol. Endocrinol. (2008) [Pubmed]
  22. Regulation of the mouse organic solute transporter {alpha}-beta, Ost{alpha}-Ostbeta, by bile acids. Frankenberg, T., Rao, A., Chen, F., Haywood, J., Shneider, B.L., Dawson, P.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  23. Identification of liver receptor homolog-1 as a novel regulator of apolipoprotein AI gene transcription. Delerive, P., Galardi, C.M., Bisi, J.E., Nicodeme, E., Goodwin, B. Mol. Endocrinol. (2004) [Pubmed]
  24. Pancreatic-duodenal homeobox 1 regulates expression of liver receptor homolog 1 during pancreas development. Annicotte, J.S., Fayard, E., Swift, G.H., Selander, L., Edlund, H., Tanaka, T., Kodama, T., Schoonjans, K., Auwerx, J. Mol. Cell. Biol. (2003) [Pubmed]
WikiGenes - Universities