The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Liver receptor homologue-1 is expressed in the adrenal and can regulate transcription of 11 beta-hydroxylase
Open accessAbstract
Liver receptor homologue-1 (LRH-1, designated NR5A2) is a mammalian homologue of Drosophila fushi tarazu factor (dFTZ-F1) and structurally belongs to the orphan nuclear receptor superfamily. LRH-1 can recognize the DNA sequence 5'-AAGGTCA-3', the canonical recognition motif for steroidogenic factor 1 (SF-1). Herein, we hypothesized that LRH-1 might play a role in the regulation of human adrenal expression of steroidogenic enzymes. To test this hypothesis, LRH-1 expression in human adult and fetal adrenal glands was examined by RT-PCR analysis. The fetal and adult adrenal glands, as well as liver and pancreas, were observed to express LRH-1 mRNA using RT-PCR. The ability of LRH-1 to enhance transcription of the gene encoding human 11 beta- hydroxylase (hCYP11B1) was then examined using the H295R adrenal cell line. LRH-1 co-transfection with hCYP11B1 luciferase promoter constructs caused a 25-fold induction of luciferase activity. Furthermore, co-transfection of a hCYP11B1 reporter construct containing a mutation in the SF-1 binding cis-element abolished the stimulatory effect of both SF-1 and LRH-1. Electrophoretic mobility shift assay (EMSA) demonstrated that LRH-1 could bind to the SF-1 response element. Taken together, our data suggested that LRH-1 is expressed in the adrenal, and can substitute for SF-1 to enhance transcription of genes encoding certain of the steroid-metabolizing enzymes. A role for LRH-1 in the regulation of adrenal or gonadal steroid hormone production should be further studied.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
SF1/NR5A1 and LRH-1/NR5A2 both contribute to the relative expression of CYP11B1 and regulate the comparative expression of CYP11B1 vs. CYP11B2.
“Orphan nuclear receptors play a critical role in CYP11B1 genetics, with SF1/NR5A1 and LRH-1/NR5A2 both contributing to the relative expression of CYP11B1 and regulating the comparative expression of CYP11B1 vs. CYP11B2 (73, 74).”
From Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies (2016) · cites this paper as [74]
The Results and Discussion report that both SF-1 and LRH-1 stimulated hCYP11B1 promoter activity in H295R cells. The paper does not establish that they regulate CYP11B1 expression relative to CYP11B2; the reported comparison is between the two receptors’ effects on CYP11B1, not between the two genes. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Biochemical and Biophysical Research Communications
Rc, A. N., On Filamentous Bacteriophage, M., Hoffmann, S., & Willbold, D. (1960) · Nature · doi:10.1038/186124d0 · Cited by 6,690
Luo, X., Ikeda, Y., & Parker, K. L. (1994) · Cell · doi:10.1016/0092-8674(94)90211-9 · Cited by 1,631 · cited 1×
“SF-1 is primarily expressed in steroidogenic tissues and plays a crucial role in regulating steroidogenic enzymes and is involved in the development of the gonads and adrenals (Lala et al. 1992, Morohashi et al. 1992, Luo et al. 1994).”
BackgroundOrphan Nuclear Receptors: From Gene to Function
Giguère, V. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.5.0378 · Cited by 871
A common trans-acting factor, Ad4-binding protein, to the promoters of steroidogenic P-450s.
Morohashi, K.-I., Honda, S., Inomata, Y., Handa, H., & Omura, T. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)37129-7 · Cited by 537
Orphan Nuclear Receptors: From Gene to Function
Giguère, V. (1999) · Endocrine Reviews · doi:10.1210/er.20.5.689 · Cited by 423
Becker-André, M., André, E., & DeLamarter, J. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.1976 · Cited by 250
Bird, I. M., Hanley, N. A., Word, R. A., Mathis, J. M., McCarthy, J. L., Mason, J. I., & Rainey, W. E. (1993) · Endocrinology · doi:10.1210/endo.133.4.8404594 · Cited by 186
Self-citationNuclear receptor regulation of cholesterol and bile acid metabolism
Repa, J. J., & Mangelsdorf, D. J. (1999) · Current Opinion in Biotechnology · doi:10.1016/s0958-1669(99)00031-2 · Cited by 179
Li, M., Xie, Y., Kong, Y., Wu, X., Zhu, L., & Wang, Y. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.44.29022 · Cited by 112
Flagged first, then by citations
Cited by
Sorted by citations
Nuclear Receptors and the Control of Metabolism
Francis, G. A., Fayard, E., Picard, F., & Auwerx, J. H. (2003) · Annual Review of Physiology · doi:10.1146/annurev.physiol.65.092101.142528 · Cited by 647
LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis.
Fayard, E., Auwerx, J., & Schoonjans, K. (2004) · Trends in Cell Biology · doi:10.1016/j.tcb.2004.03.008 · Cited by 445
SF-1 a key player in the development and differentiation of steroidogenic tissues
Val, P., Lefrançois‐Martinez, A., VEYSSIERE, G., & Martinez, A. (2003) · Nuclear Receptor · doi:10.1186/1478-1336-1-8 · Cited by 255
International Union of Pharmacology. LXVI. Orphan Nuclear Receptors
Benoit, G., Cooney, A. J., Giguère, V., Ingraham, H. A., Lazar, M., Muscat, G. E. O., Perlmann, T., Renaud, J., Schwabe, J. W. R., Sladek, F. M., et al. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.4.10 · Cited by 238
Liver Receptor Homologue-1 (LRH-1) Regulates Expression of Aromatase in Preadipocytes
Clyne, C. D., Speed, C. J., Zhou, J., & Simpson, E. R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201117200 · Cited by 233
Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP
Ortlund, E. A., Lee, Y., Solomon, I. H., Hager, J., Safi, R., Choi, Y., Guan, Z., Tripathy, A., Raetz, C. R. H., McDonnell, D. P., et al. (2005) · Nature Structural & Molecular Biology · doi:10.1038/nsmb910 · Cited by 203
Molecular mechanisms of DAX1 action
Iyer, A. K., & McCabe, E. R. B. (2004) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2004.07.018 · Cited by 193
Sewer, M. B., & Waterman, M. R. (2003) · Microscopy Research and Technique · doi:10.1002/jemt.10339 · Cited by 179
Suzuki, T., Kasahara, M., Yoshioka, H., Morohashi, K.-I., & Umesono, K. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.23.1.238-249.2003 · Cited by 153
Sirianni, R., Seely, J. B., Attia, G., Stocco, D., Carr, B., Pezzi, V., & Rainey, W. (2002) · Journal of Endocrinology · doi:10.1677/joe.0.174r013 · Cited by 137
Self-citationMartin, L. J., & Tremblay, J. (2004) · Endocrinology · doi:10.1210/en.2004-0859 · Cited by 125
Mueller, M., Cima, I., Noti, M., Fuhrer, A. C., Jakob, S., Dubuquoy, L., Schoonjans, K., & Brunner, T. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060357 · Cited by 126
Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies
Midzak, A., & Papadopoulos, V. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00106 · Cited by 114
Gummow, B. M., Scheys, J. O., Cancelli, V. R., & Hammer, G. D. (2006) · Molecular Endocrinology · doi:10.1210/me.2005-0461 · Cited by 114
Bland, M. L., Fowkes, R. C., & Ingraham, H. A. (2004) · Molecular Endocrinology · doi:10.1210/me.2003-0333 · Cited by 105
Cholesterol: A Gatekeeper of Male Fertility?
Sèdes, L., Thirouard, L., Maqdasy, S., Garcia, M., Caira, F., Lobaccaro, J. A., Beaudoin, C., & Volle, D. H. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00369 · Cited by 101
Li, Y., Choi, M., Suino, K., Kovach, A., Daugherty, J., Kliewer, S. A., & Xu, H. E. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501204102 · Cited by 95
DAX1 origin, function, and novel role
Niakan, K. K., & McCabe, E. R. B. (2005) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2005.07.019 · Cited by 98
Peng, N., Kim, J. W., Rainey, W. E., Carr, B. R., & Attia, G. R. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030880 · Cited by 85
Self-citationMartin, L. J., Taniguchi, H., Robert, N. M., Simard, J., Tremblay, J., & Viger, R. S. (2005) · Molecular Endocrinology · doi:10.1210/me.2004-0257 · Cited by 84
Wu, X., Chen, L., Brown, C. A., Yan, C., & Matzuk, M. M. (2004) · Molecular Endocrinology · doi:10.1210/me.2003-0399 · Cited by 81
The interrelationship between bile acid and vitamin A homeostasis
Saeed, A., Hoekstra, M., Hoeke, M. O., Heegsma, J., & Faber, K. N. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2017.01.007 · Cited by 85
Yazawa, T., Inanoka, Y., Mizutani, T., Kuribayashi, M., Umezawa, A., & Miyamoto, K. (2009) · Endocrinology · doi:10.1210/en.2008-1310 · Cited by 75
Cholesterol and male fertility: What about orphans and adopted?
Maqdasy, S., Baptissart, M., Vega, A., Baron, S., Lobaccaro, J. A., & Volle, D. H. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.06.011 · Cited by 78
Roumaud, P., & Martin, L. J. (2015) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2015-0046 · Cited by 70
Evolution of the repertoire of nuclear receptor binding sites in genomes
Cotnoir‐White, D., Laperrière, D., & Mader, S. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.10.021 · Cited by 65
Kim, J. W., Peng, N., Rainey, W. E., Carr, B. R., & Attia, G. R. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031599 · Cited by 65
Self-citationKramer, H. B., Lai, C., Patel, H., Periyasamy, M., Lin, M., Feller, S. M., Fuller-Pace, F. V., Meek, D. W., Ali, S., & Buluwela, L. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv948 · Cited by 59
Therapeutic potential of Liver Receptor Homolog-1 modulators
Lazarus, K. A., Wijayakumara, D., Chand, A. L., Simpson, E. R., & Clyne, C. D. (2012) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2011.12.017 · Cited by 58
Weck, J., & Mayo, K. E. (2006) · Molecular Endocrinology · doi:10.1210/me.2005-0199 · Cited by 58
Transcriptional Regulation of Adrenocortical Steroidogenic Gene Expression
Sewer, M. B., Dammer, E. B., & Jagarlapudi, S. (2007) · Drug Metabolism Reviews · doi:10.1080/03602530701498828 · Cited by 55
Miki, Y., Clyne, C. D., Suzuki, T., Moriya, T., Shibuya, R., Nakamura, Y., Ishida, T., Yabuki, N., Kitada, K., Hayashi, S., et al. (2006) · Cancer Letters · doi:10.1016/j.canlet.2005.11.038 · Cited by 55
Yazawa, T., Kawabe, S., Inaoka, Y., Okada, R., Mizutani, T., Imamichi, Y., Ju, Y., Yamazaki, Y., Usami, Y., Kuribayashi, M., et al. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.11.025 · Cited by 53
Xu, P., Liu, Y.-Q., Shan, S., Kong, Y., Zhou, Q., Li, M., Ding, J., Xie, Y., & Wang, Y. (2004) · Molecular Endocrinology · doi:10.1210/me.2003-0334 · Cited by 45
Orphan Nuclear Receptors as Targets for Drug Development
Mukherjee, S., & Mani, S. (2010) · Pharmaceutical Research · doi:10.1007/s11095-010-0117-7 · Cited by 42
Yazawa, T., Imamichi, Y., Sekiguchi, T., Miyamoto, K., Uwada, J., Khan, M. R. I., Suzuki, N., Umezawa, A., & Taniguchi, T. (2019) · BioMed Research International · doi:10.1155/2019/8973076 · Cited by 38
LRH-1 and Nanog regulate Dax1 transcription in mouse embryonic stem cells
Kelly, V. R., & Hammer, G. D. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.10.003 · Cited by 37
Yazawa, T., Imamichi, Y., & Miyamoto, K. (2015) · ZOOLOGICAL SCIENCE · doi:10.2108/zs140237 · Cited by 34
Sugawara, T., Sakuragi, N., & Minakami, H. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06601 · Cited by 32
Bolado‐Carrancio, A., Riancho, J. A., Sainz, J., & Rodríguez-Rey, J. C. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.03.010 · Cited by 21
Sphingosine-1-phosphate regulates the expression of the liver receptor homologue-1
Hadizadeh, S., King, D. N., Shah, S., & Sewer, M. B. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2007.11.030 · Cited by 21
Differentiation of mesenchymal stem cells into gonad and adrenal steroidogenic cells
Yazawa, T. (2014) · World Journal of Stem Cells · doi:10.4252/wjsc.v6.i2.203 · Cited by 16
Regulation of Steroidogenesis by p53 in Macaque Granulosa Cells and H295R Human Adrenocortical Cells
Cherian‐Shaw, M., Das, R., VandeVoort, C. A., & Chaffin, C. L. (2004) · Endocrinology · doi:10.1210/en.2004-0253 · Cited by 16
Martinez, A., Val, P., Sahut‐Barnola, I., Aigueperse, C., VEYSSIERE, G., & Lefrançois‐Martinez, A. (2003) · Endocrinology · doi:10.1210/en.2002-220825 · Cited by 17
Hu, C., Su, H. W., Wu, F., & Ding, H. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.9468 · Cited by 13
Expression profiling of liver receptor homologue 1 (LRH-1) in mouse tissues using tissue microarray
Higashiyama, H., Kinoshita, M., & Asano, S. (2007) · Journal of Molecular Histology · doi:10.1007/s10735-007-9077-6 · Cited by 13
França, M. M., Ferraz‐de‐Souza, B., Lerário, A. M., Fragoso, M. C. B. V., & Lotfi, C. F. P. (2015) · BioMed Research International · doi:10.1155/2015/841784 · Cited by 12
Widespread expression of liver receptor homolog 1 in mouse brain.
Grgurevič, N., Tobet, S. A., & Majdič, G. (2005) · PubMed · Cited by 12
FXRα modulates leydig cell endocrine function in mouse
Holota, H., Thirouard, L., Monrose, M., Garcia, M., Haze, A. D., Saru, J., Caira, F., Beaudoin, C., & Volle, D. H. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.110995 · Cited by 11
The Medicinal Chemistry and Therapeutic Potential of LRH-1 Modulators
Lang, A., Isigkeit, L., Schubert‐Zsilavecz, M., & Merk, D. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01663 · Cited by 9
Morales, A., Vilchis, F., Chávez, B. A., Morimoto, S., Chan, C. H. F., Robles‐Díaz, G., & Díaz‐Sánchez, V. (2008) · Pancreas · doi:10.1097/mpa.0b013e318168dd8c · Cited by 9
LRH-1 May Rescue SF-1 Deficiency for Steroidogenesis: An in vitro and in vivo Study
Camats, N., Audı́, L., Fernández‐Cancio, M., Andaluz, P., Mullis, P. E., Carrascosa, A., & Flück, C. E. (2015) · Sexual Development · doi:10.1159/000381575 · Cited by 7
Kanno, M., Yazawa, T., Kawabe, S., Imamichi, Y., Usami, Y., Ju, Y., Matsumura, T., Mizutani, T., Fujieda, S., & Miyamoto, K. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.03.016 · Cited by 5
Viger, R. S., Bouchard, M. F., & Tremblay, J. (2024) · Journal of Endocrinology · doi:10.1530/joe-24-0087 · Cited by 4
Molecular characterization and expression analysis of the Lrh-1 gene in Chinese Hu sheep
Wang, L., Zhang, W., Ji, J. L., Gao, Q. X., Xiao, S., & Wang, F. (2013) · Genetics and Molecular Research · doi:10.4238/2013.may.6.2 · Cited by 4
Wang, S., Lan, F., ZHUANG, Y.-P., Li, H., Huang, L., Zheng, D.-Z., Jian, Z. E. N. G., Li-Hong, D. O. N. G., Zhu, Z., & Fu, J. (2006) · Acta Genetica Sinica · doi:10.1016/s0379-4172(06)60122-4 · Cited by 4
Chen, X., Tong, X., Xie, Y., Wang, Y., Ma, J., Gao, D., Wu, H., & Chen, H. (2005) · Protein Expression and Purification · doi:10.1016/j.pep.2005.06.005 · Cited by 4
Gene expression profile in liver of hB1F transgenic mice
Wang, S. (2004) · World Journal of Gastroenterology · doi:10.3748/wjg.v10.i20.3006 · Cited by 2
Kleine, B., & Rossmanith, W. G. (2020) · Springer eBooks · doi:10.1007/978-3-662-58502-3_6 · Cited by 1
NR5A2: a regulator of glucose metabolism
Romagosa, M. Á. Q. (2011) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) · Cited by 1
Hoeke, M. O. (2013) · University of Groningen research database (University of Groningen / Centre for Information Technology) · Cited by 1
Hormones from Mevalonate: Juvenile Hormone and Steroid Hormones
Kleine, B., & Rossmanith, W. G. (2016) · Springer eBooks · doi:10.1007/978-3-319-15060-4_6
Analyse de la régulation de l'homéostasie des acides biliaires au sein des testicules
Holota, H. (2024) · theses.fr (ABES) · doi:10.70675/87a97831z9d93z48dazb8b7z8e7a929fc132
BindingDB Entry 50018307: The Medicinal Chemistry and Therapeutic Potential of LRH-1 Modulators.
BindingDB (2024) · UC San Diego · doi:10.7270/q2d79gm1
Metadata
- Authors
- Wang, Z., Bassett, M., & Rainey, W.
- Affiliations
- The University of Texas at Dallas (US)
- Venue
- Journal of Molecular Endocrinology
- Publisher
- Bioscientifica
- Published
- 2001-10-01
- Volume
- 27
- Issue
- 2
- Pages
- 255-258
- ISSN
- 0952-5041 (ISSN-L)
- 1479-6813
- OpenAlex
- W2054729369
- Cited by
- 63
- References
- 9
- Citations by year
- 2024: 2 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 5 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Washington
- University of Texas Southwestern Medical Center
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 43140)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- LRH-1, NR5A2, adrenal gland, 11β-hydroxylase, CYP11B1, steroidogenic factor 1, transcriptional regulation, steroidogenic enzymes, orphan nuclear receptor, adrenal steroidogenesis, fetal adrenal
- MeSH terms
- Adrenal Glands, Animals, Base Sequence, Binding Sites, Cell Line, DNA, DNA-Binding Proteins, Fetus, Humans, Luciferases, Mutation, RNA, Messenger, Steroid 11-beta-Hydroxylase, Transcription Factors, Transcription, Genetic, Transfection, Gene Expression Regulation, Enzymologic, Receptors, Cytoplasmic and Nuclear, Homeodomain Proteins, Fushi Tarazu Transcription Factors, Steroidogenic Factor 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
