Gene Symbol: Nr5a1
Description: nuclear receptor subfamily 5, group A, member 1
Alias: Ad4BP/SF-1, Ad4bp, Ftzf1, Sf-1, steroidogenic factor 1, STF-1, adrenal 4-binding protein, fushi tarazu factor homolog 1, steroid hormone receptor Ad4BP
Species: rat
Products:     Nr5a1

Top Publications

  1. Lee F, Faivre E, Suzawa M, Lontok E, Ebert D, Cai F, et al. Eliminating SF-1 (NR5A1) sumoylation in vivo results in ectopic hedgehog signaling and disruption of endocrine development. Dev Cell. 2011;21:315-27 pubmed publisher
    ..Here, we permanently eliminated SF-1/NR5A1 sumoylation in mice (Sf-1(K119R, K194R, or 2KR)) and found that Sf-1(2KR/2KR) mice failed to phenocopy a simple ..
  2. Achermann J, Ozisik G, Ito M, Orun U, Harmanci K, Gurakan B, et al. Gonadal determination and adrenal development are regulated by the orphan nuclear receptor steroidogenic factor-1, in a dose-dependent manner. J Clin Endocrinol Metab. 2002;87:1829-33 pubmed
    The orphan nuclear receptor steroidogenic factor-1 (SF-1, NR5A1) regulates the transcription of multiple genes involved in steroidogenesis, reproduction, and male sexual differentiation...
  3. Kimura R, Yoshii H, Nomura M, Kotomura N, Mukai T, Ishihara S, et al. Identification of novel first exons in Ad4BP/SF-1 (NR5A1) gene and their tissue- and species-specific usage. Biochem Biophys Res Commun. 2000;278:63-71 pubmed
    It has been demonstrated that the mammalian Ad4BP/SF-1 (NR5A1) gene is regulated precisely in sex, tissue, and developmental stage specific manners...
  4. Lu C, Yang W, Chen M, Liu T, Yang J, Tan P, et al. Inhibin A inhibits follicle-stimulating hormone (FSH) action by suppressing its receptor expression in cultured rat granulosa cells. Mol Cell Endocrinol. 2009;298:48-56 pubmed publisher
    ..Inhibin A was also capable of suppressing FSH-induced expression of steroidogenic factor 1 (SF-1) and androgen receptor, but stimulating DAX-1 expression in the culture...
  5. Chang L, Wun W, Wang P. Mechanisms of inhibition of dehydroepiandrosterone upon corticosterone release from rat zona fasciculata-reticularis cells. J Cell Biochem. 2008;104:359-68 pubmed
  6. Karpova T, Maran R, Presley J, Scherrer S, Tejada L, Heckert L. Transgenic rescue of SF-1-null mice. Ann N Y Acad Sci. 2005;1061:55-64 pubmed
    b>Steroidogenic factor 1 (SF-1, Nr5a1, and Ad4bp) is an orphan nuclear receptor required for adrenal and gonad development and endocrine regulation...
  7. Chen M, Wang S, Kan S, Tsai S, Wu Y, Wang P. Stimulatory effects of propylthiouracil on pregnenolone production through upregulation of steroidogenic acute regulatory protein expression in rat granulosa cells. Toxicol Sci. 2010;118:667-74 pubmed publisher
    ..The regulation of negative feedback on speeding the cholesterol transportation and pregnenolone conversion after a 16-h PTU treatment may be the mechanism explaining PTU's inhibition of progesterone production in rat granulosa cells. ..
  8. Talamillo A, Herboso L, Pirone L, P rez C, Gonz lez M, S nchez J, et al. Scavenger receptors mediate the role of SUMO and Ftz-f1 in Drosophila steroidogenesis. PLoS Genet. 2013;9:e1003473 pubmed publisher
  9. Jacobs S, Coss D, McGillivray S, Mellon P. Nuclear factor Y and steroidogenic factor 1 physically and functionally interact to contribute to cell-specific expression of the mouse Follicle-stimulating hormone-beta gene. Mol Endocrinol. 2003;17:1470-83 pubmed
    ..This study is the first to demonstrate the presence of basal FSH beta protein in L beta T2 cells and to identify specific elements within the FSH beta promoter that contribute to basal and cell-specific expression of the gene. ..

More Information


  1. Sirianni R, Chimento A, Malivindi R, Mazzitelli I, Ando S, Pezzi V. Insulin-like growth factor-I, regulating aromatase expression through steroidogenic factor 1, supports estrogen-dependent tumor Leydig cell proliferation. Cancer Res. 2007;67:8368-77 pubmed and phosphorylated levels of transcription factors cyclic AMP-responsive element binding protein and steroidogenic factor 1 (SF-1) were higher in tumor samples...
  2. Yazawa T, Mizutani T, Yamada K, Kawata H, Sekiguchi T, Yoshino M, et al. Involvement of cyclic adenosine 5'-monophosphate response element-binding protein, steroidogenic factor 1, and Dax-1 in the regulation of gonadotropin-inducible ovarian transcription factor 1 gene expression by follicle-stimulating hormone in ovarian. Endocrinology. 2003;144:1920-30 pubmed
    ..Deletion and mutational analyses indicated that two response elements, including a steroidogenic factor 1 (SF-1) site and a cAMP response element (CRE), are required for the activation of the gene by FSH...
  3. Nomura M, Bartsch S, Nawata H, Omura T, Morohashi K. An E box element is required for the expression of the ad4bp gene, a mammalian homologue of ftz-f1 gene, which is essential for adrenal and gonadal development. J Biol Chem. 1995;270:7453-61 pubmed
    b>Ad4BP, also known as SF-1, is a cell type-specific transcription factor regulating all the steroidogenic P-450 genes...
  4. Bianconcini A, Lupo A, Capone S, Quadro L, Monti M, Zurlo D, et al. Transcriptional activity of the murine retinol-binding protein gene is regulated by a multiprotein complex containing HMGA1, p54 nrb/NonO, protein-associated splicing factor (PSF) and steroidogenic factor 1 (SF1)/liver receptor homologue 1 (LRH-1). Int J Biochem Cell Biol. 2009;41:2189-203 pubmed publisher
    ..b>Steroidogenic factor 1 (SF1) or the related liver receptor homologue 1 (LRH-1) are also associated with this complex upon cAMP-..
  5. Kashimada K, Svingen T, Feng C, Pelosi E, Bagheri Fam S, Harley V, et al. Antagonistic regulation of Cyp26b1 by transcription factors SOX9/SF1 and FOXL2 during gonadal development in mice. FASEB J. 2011;25:3561-9 pubmed publisher
    ..These data support the hypothesis that SOX9 and SF1 ensure the male fate of germ cells by up-regulating Cyp26b1 and that FOXL2 acts to antagonize Cyp26b1 expression in ovaries. ..
  6. Knower K, Kelly S, Ludbrook L, Bagheri Fam S, Sim H, Bernard P, et al. Failure of SOX9 regulation in 46XY disorders of sex development with SRY, SOX9 and SF1 mutations. PLoS ONE. 2011;6:e17751 pubmed publisher
    In human embryogenesis, loss of SRY (sex determining region on Y), SOX9 (SRY-related HMG box 9) or SF1 (steroidogenic factor 1) function causes disorders of sex development (DSD)...
  7. Lalli E, Ohe K, Hindelang C, Sassone Corsi P. Orphan receptor DAX-1 is a shuttling RNA binding protein associated with polyribosomes via mRNA. Mol Cell Biol. 2000;20:4910-21 pubmed
    ..Mutations in DAX-1 found in AHC-HHG patients significantly impair RNA binding. These findings reveal that DAX-1 plays multiple regulatory roles at the transcriptional and posttranscriptional levels. ..
  8. Wood M, Mukherjee P, Toocheck C, Walker W. Upstream stimulatory factor induces Nr5a1 and Shbg gene expression during the onset of rat Sertoli cell differentiation. Biol Reprod. 2011;85:965-76 pubmed publisher
    ..USF2 DNA-binding activity also increased at 11 days for the promoters of four potential target genes, Fshr, Gata4, Nr5a1, and Shbg...
  9. Fabbri H, de Andrade J, Soardi F, de Calais F, Petroli R, Maciel Guerra A, et al. The novel p.Cys65Tyr mutation in NR5A1 gene in three 46,XY siblings with normal testosterone levels and their mother with primary ovarian insufficiency. BMC Med Genet. 2014;15:7 pubmed publisher
    ..Nuclear receptor subfamily 5, group A, member 1 gene (NR5A1) encodes steroidogenic factor 1 (SF1), a transcription factor that is involved in gonadal development and regulates adrenal ..
  10. Curtin D, Ferris H, Hakli M, Gibson M, Janne O, Palvimo J, et al. Small nuclear RING finger protein stimulates the rat luteinizing hormone-beta promoter by interacting with Sp1 and steroidogenic factor-1 and protects from androgen suppression. Mol Endocrinol. 2004;18:1263-76 pubmed
    ..It has been hypothesized that the transcription factors binding to these regions, Sp1, Egr-1, and steroidogenic factor 1 (SF-1), may interact directly or indirectly via a coactivator...
  11. Swartz J, Ciarlo R, Guo M, Abrha A, Weaver B, Diamond D, et al. A 46,XX Ovotesticular Disorder of Sex Development Likely Caused by a Steroidogenic Factor-1 (NR5A1) Variant. Horm Res Paediatr. 2017;87:191-195 pubmed publisher
    A variant in steroidogenic factor-1 (SF-1, encoded by the gene NR5A1), p.Arg92Trp, has recently been reported in multiple families with 46,XX ovotesticular or testicular disorders of sex development (DSD)...
  12. Pulichino A, Vallette Kasic S, Tsai J, Couture C, Gauthier Y, Drouin J. Tpit determines alternate fates during pituitary cell differentiation. Genes Dev. 2003;17:738-47 pubmed
    ..These data suggest that antagonism between Tpit and SF1 may play a role in establishment of POMC and gonadotroph lineages and that these lineages may arise from common precursors. ..
  13. Zheng W, Jimenez Linan M, Rubin B, Halvorson L. Anterior pituitary gene expression with reproductive aging in the female rat. Biol Reprod. 2007;76:1091-102 pubmed
    ..for gonadotroph function, including 1) steroid hormone receptors (Esr and Pgr), 2) orphan nuclear receptors [Nr5a1 (steroidogenic factor-1) and Nr5a2 (liver receptor homologue-1)], and 3) pituitary-derived polypeptides (activin, ..
  14. Catalano S, Malivindi R, Giordano C, Gu G, Panza S, Bonofiglio D, et al. Farnesoid X receptor, through the binding with steroidogenic factor 1-responsive element, inhibits aromatase expression in tumor Leydig cells. J Biol Chem. 2010;285:5581-93 pubmed publisher
    ..mobility shift, and chromatin immunoprecipitation analysis reveal that FXR is able to compete with steroidogenic factor 1 in binding to a common sequence present in the aromatase promoter region interfering negatively with its ..
  15. Winnay J, Hammer G. Adrenocorticotropic hormone-mediated signaling cascades coordinate a cyclic pattern of steroidogenic factor 1-dependent transcriptional activation. Mol Endocrinol. 2006;20:147-66 pubmed
    b>Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that has emerged as a critical mediator of endocrine function at multiple levels of the hypothalamic-pituitary-steroidogenic axis...
  16. Lee H, Pazin D, Kahlon R, Correa S, Albrecht K. Novel markers of early ovarian pre-granulosa cells are expressed in an Sry-like pattern. Dev Dyn. 2009;238:812-25 pubmed publisher
  17. Shen J, Ingraham H. Regulation of the orphan nuclear receptor steroidogenic factor 1 by Sox proteins. Mol Endocrinol. 2002;16:529-40 pubmed
    b>Steroidogenic factor 1 (SF-1) is an essential factor in endocrine proliferation and gene expression...
  18. Li D, Urs A, Allegood J, Leon A, Merrill A, Sewer M. Cyclic AMP-stimulated interaction between steroidogenic factor 1 and diacylglycerol kinase theta facilitates induction of CYP17. Mol Cell Biol. 2007;27:6669-85 pubmed
    ..adrenocorticotropin (ACTH) activates CYP17 transcription by promoting the binding of the nuclear receptor steroidogenic factor 1 (SF1) (Ad4BP, NR5A1) to the promoter...
  19. Lynch J, Lala D, Peluso J, Luo W, Parker K, White B. Steroidogenic factor 1, an orphan nuclear receptor, regulates the expression of the rat aromatase gene in gonadal tissues. Mol Endocrinol. 1993;7:776-86 pubmed
    ..steroid hydroxylases, we identified and characterized a transcriptional regulatory protein, designated steroidogenic factor 1 (SF-1), that contributes to the coordinate expression in adrenocortical cells...
  20. Harikai N. Characteristic induction of steroidogenic factor 1 (SF-1) and DAX-1 and enhanced expression of glucocorticoid synthesis-related genes in adrenals from spontaneously hypertensive rats. Gen Physiol Biophys. 2012;31:39-45 pubmed publisher
    ..P450 side chain cleavage enzyme (P450scc) and 11?-hydroxylase (P450c11), and the transcription factors of steroidogenic factor 1 (SF-1), which stimulates expression of the above gene, and DAX-1 (dosage-sensitive sex reversal-adrenal ..
  21. Baetens D, Stoop H, Peelman F, Todeschini A, Rosseel T, Coppieters F, et al. NR5A1 is a novel disease gene for 46,XX testicular and ovotesticular disorders of sex development. Genet Med. 2017;19:367-376 pubmed publisher
    ..We identified a novel heterozygous NR5A1 mutation, c.274C>T p.(Arg92Trp), in three unrelated patients...
  22. Bashamboo A, Donohoue P, Vilain E, Rojo S, Calvel P, Seneviratne S, et al. A recurrent p.Arg92Trp variant in steroidogenic factor-1 (NR5A1) can act as a molecular switch in human sex development. Hum Mol Genet. 2016;25:3446-3453 pubmed publisher
    ..Steroidogenic factor-1 (known as NR5A1) is a key regulator of reproductive development and function...
  23. Wang W, Sun Y, Guo Y, Cai P, Li Y, Liu J, et al. Continuous soy isoflavones exposure from weaning to maturity induces downregulation of ovarian steroidogenic factor 1 gene expression and corresponding changes in DNA methylation pattern. Toxicol Lett. 2017;281:175-183 pubmed publisher
    ..In addition, DNA methylation might play a role in the downregulation of SF-1 gene expression induced by soy isoflavones...
  24. Bland M, Fowkes R, Ingraham H. Differential requirement for steroidogenic factor-1 gene dosage in adrenal development versus endocrine function. Mol Endocrinol. 2004;18:941-52 pubmed
    ..Our findings underscore the need for full SF-1 gene dosage early in adrenal development, but not in the adult adrenal, where compensatory mechanisms restore near normal function. ..
  25. Kawabe K, Shikayama T, Tsuboi H, Oka S, Oba K, Yanase T, et al. Dax-1 as one of the target genes of Ad4BP/SF-1. Mol Endocrinol. 1999;13:1267-84 pubmed
    ..In recent studies, DAX-1 was reported to function as a transcriptional suppressor of Ad4BP/SF-1, a critical transcription factor in gonadal and adrenal differentiation...
  26. Kabe Y, Goto M, Shima D, Imai T, Wada T, Morohashi K, et al. The role of human MBF1 as a transcriptional coactivator. J Biol Chem. 1999;274:34196-202 pubmed
    ..Both isoforms bound to TBP and Ad4BP/SF-1, a mammalian counterpart of FTZ-F1, and mediated Ad4BP/SF-1-dependent transcriptional activation...
  27. Schepers G, Wilson M, Wilhelm D, Koopman P. SOX8 is expressed during testis differentiation in mice and synergizes with SF1 to activate the Amh promoter in vitro. J Biol Chem. 2003;278:28101-8 pubmed
  28. Falender A, Lanz R, Malenfant D, Belanger L, Richards J. Differential expression of steroidogenic factor-1 and FTF/LRH-1 in the rodent ovary. Endocrinology. 2003;144:3598-610 pubmed
    Steroidogenic factor-1 (SF-1) (NR5A1) is an orphan nuclear receptor that plays a premier role in ovarian organogenesis...
  29. Park S, Meeks J, Raverot G, Pfaff L, Weiss J, Hammer G, et al. Nuclear receptors Sf1 and Dax1 function cooperatively to mediate somatic cell differentiation during testis development. Development. 2005;132:2415-23 pubmed
    ..Thus, although Sf1 and Dax1 function as transcriptional antagonists for many target genes in vitro, they act independently or cooperatively in vivo during male gonadal development. ..
  30. Rosewich H, Ohlenbusch A, Gartner J. Genetic and clinical aspects of Zellweger spectrum patients with PEX1 mutations. J Med Genet. 2005;42:e58 pubmed
    ..To analyse the PEX1 gene, the most common cause for peroxisome biogenesis disorders (PBD), in a consecutive series of patients with Zellweger spectrum...
  31. Jeyasuria P, Ikeda Y, Jamin S, Zhao L, de Rooij D, Themmen A, et al. Cell-specific knockout of steroidogenic factor 1 reveals its essential roles in gonadal function. Mol Endocrinol. 2004;18:1610-9 pubmed
    Knockout (KO) mice lacking the orphan nuclear receptor steroidogenic factor 1 (SF-1, officially designated Nr5a1) have a compound endocrine phenotype that includes adrenal and gonadal agenesis, impaired expression of pituitary ..
  32. Xiao Y, Hardy D, Sottas C, Li X, Ge R. Inhibition of LH-stimulated androgen production in rat immature Leydig cells: Effects on nuclear receptor steroidogenic factor 1 by FGF2. Growth Factors. 2010;28:1-9 pubmed publisher
    ..steroidogenic enzymes, inhibited the expressions of steroidogenic acute regulatory (StAR) protein and steroidogenic factor 1 (Nr5a1) in LH-stimulated ILCs...
  33. Cai K, Sewer M. cAMP-stimulated transcription of DGK? requires steroidogenic factor 1 and sterol regulatory element binding protein 1. J Lipid Res. 2013;54:2121-32 pubmed publisher
    ..We have previously shown that PA is a ligand for the nuclear receptor steroidogenic factor 1 (SF1) and that cAMP-stimulated expression of SF1 target genes requires DGK?...
  34. Kennell J, O Leary E, Gummow B, Hammer G, MacDougald O. T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors. Mol Cell Biol. 2003;23:5366-75 pubmed
    ..the alpha-inhibin promoter through functional and physical interactions with the orphan nuclear receptor steroidogenic factor 1 (SF-1)...
  35. Buaas F, Val P, Swain A. The transcription co-factor CITED2 functions during sex determination and early gonad development. Hum Mol Genet. 2009;18:2989-3001 pubmed publisher
    ..This highlights the gene dosage sensitivity of the pathway's effect on Sry levels and embryonic gonad development...
  36. Igarashi M, Takasawa K, Hakoda A, Kanno J, Takada S, Miyado M, et al. Identical NR5A1 Missense Mutations in Two Unrelated 46,XX Individuals with Testicular Tissues. Hum Mutat. 2017;38:39-42 pubmed publisher
    ..Although mutations in NR5A1 are known to cause 46,XY gonadal dysgenesis and 46,XX ovarian insufficiency, such mutations have not been ..
  37. Huang Y, Lee C, Tai P, Yen C, Liao C, Chen W, et al. Indirect regulation of human dehydroepiandrosterone sulfotransferase family 1A member 2 by thyroid hormones. Endocrinology. 2006;147:2481-9 pubmed
    ..SULT2A1 has been reported to be regulated by the two transcription factors, steroidogenic factor 1 (SF1) and GATA, in the human adrenal gland. T(3) induced a 2.5- to 3...
  38. Wilson M, Jeyasuria P, Parker K, Koopman P. The transcription factors steroidogenic factor-1 and SOX9 regulate expression of Vanin-1 during mouse testis development. J Biol Chem. 2005;280:5917-23 pubmed
    ..Our findings account for the sex- and cell-type-specific expression of Vanin-1 in the developing mouse gonad in vivo, which we suggest is required to provide an appropriate environment for male germ cell development. ..
  39. Laverrière J, Granger A, Pincas H, Ngô Muller V, Bleux C, Tixier Vidal A, et al. [An ambiguous role of steroidogenic factor 1 in the rat GnRH receptor gene expression. Lessons from transgenic mice]. J Soc Biol. 2004;198:73-9 pubmed
  40. Lai W, Yeh Y, Fang W, Wu L, Harada N, Wang P, et al. Calcineurin and CRTC2 mediate FSH and TGF?1 upregulation of Cyp19a1 and Nr5a in ovary granulosa cells. J Mol Endocrinol. 2014;53:259-70 pubmed publisher
    ..response elements for CREB and nuclear receptor NR5A subfamily liver receptor homolog 1 (LRH1/NR5A2) and steroidogenic factor 1 (SF1/NR5A1), and that the Nr5a2 promoter also has a potential CREB-binding site...
  41. Babu P, Bavers D, Beuschlein F, Shah S, Jeffs B, Jameson J, et al. Interaction between Dax-1 and steroidogenic factor-1 in vivo: increased adrenal responsiveness to ACTH in the absence of Dax-1. Endocrinology. 2002;143:665-73 pubmed
    ..These results are consistent with a model in which Dax-1 functions to inhibit SF-1-mediated steroidogenesis in vivo. ..
  42. Yu C, Li P. In vivo inhibition of steroidogenic acute regulatory protein expression by dexamethasone parallels induction of the negative transcription factor DAX-1. Endocrine. 2006;30:313-23 pubmed
  43. Kawajiri K, Ikuta T, Suzuki T, Kusaka M, Muramatsu M, Fujieda K, et al. Role of the LXXLL-motif and activation function 2 domain in subcellular localization of Dax-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1). Mol Endocrinol. 2003;17:994-1004 pubmed
    ..gene 1 (Dax-1, NR0B1) is an orphan nuclear receptor that represses transcription by Ad4 binding protein/steroidogenic factor 1 (Ad4BP/SF-1, NR5A1)...
  44. Gut P, Huber K, Lohr J, Brühl B, Oberle S, Treier M, et al. Lack of an adrenal cortex in Sf1 mutant mice is compatible with the generation and differentiation of chromaffin cells. Development. 2005;132:4611-9 pubmed
    ..Our results suggest that cortical cues are not essential for determining chromaffin cell fate, but may be required for proper migration of SA progenitors to and/or colonization of the adrenal anlage...