Zhang Y, Luo XY, Wu DH, Xu Y. ROR nuclear receptors: structures, related diseases, and drug discovery. Acta Pharmacol Sin. 2015;36:71–87.

Article  PubMed  Google Scholar 

Wärnmark A, Treuter E, Wright AP, Gustafsson JA. Activation functions 1 and 2 of nuclear receptors: molecular strategies for transcriptional activation. Mol Endocrinol. 2003;17:1901–9.

Article  PubMed  Google Scholar 

Sar P. Nuclear receptor: structure and function. Prog Mol Biol Transl Sci. 2023;196:209–27.

Article  CAS  PubMed  Google Scholar 

Weikum ER, Liu X, Ortlund EA. The nuclear receptor superfamily: a structural perspective. Protein Sci. 2018;27:1876–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Giguère V. Orphan nuclear receptors: from gene to function. Endocr Rev. 1999;20:689–725.

PubMed  Google Scholar 

Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov. 2006;5:993–96.

Article  CAS  PubMed  Google Scholar 

Fayard E, Auwerx J, Schoonjans K. LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis. Trends Cell Biol. 2004;14:250–60.

Article  CAS  PubMed  Google Scholar 

Zerlotin R, Arconzo M, Piccinin E, Moschetta A. Another one bites the gut: nuclear receptor LRH-1 in intestinal regeneration and cancer. Cancers. 2021;13:896.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sun Y, Demagny H, Schoonjans K. Emerging functions of the nuclear receptor LRH-1 in liver physiology and pathology. Biochim Biophys Acta Mol Basis Dis. 2021;1867:166145.

Article  CAS  PubMed  Google Scholar 

Michalek S, Brunner T. Nuclear-mitochondrial crosstalk: on the role of the nuclear receptor liver receptor homolog-1 (NR5A2) in the regulation of mitochondrial metabolism, cell survival, and cancer. IUBMB Life. 2021;73:592–610.

Article  CAS  PubMed  Google Scholar 

Yazawa T, Imamichi Y, Miyamoto K, Khan MR, Uwada J, Umezawa A, et al. Regulation of steroidogenesis, development, and cell differentiation by steroidogenic factor-1 and liver receptor homolog-1. Zool Sci. 2015;32:323–30.

Article  CAS  Google Scholar 

Mouzat K, Baron S, Marceau G, Caira F, Sapin V, Volle DH, et al. Emerging roles for LXRs and LRH-1 in female reproduction. Mol Cell Endocrinol. 2013;368:47–58.

Article  CAS  PubMed  Google Scholar 

Sandhu N, Rana S, Meena K. Nuclear receptor subfamily 5 group A member 2 (NR5A2): role in health and diseases. Mol Biol Rep. 2021;48:8155–70.

Article  CAS  PubMed  Google Scholar 

Meinsohn M-C, Smith OE, Bertolin K, Murphy BD. The orphan nuclear receptors steroidogenic factor-1 and liver receptor homolog-1: structure, regulation, and essential roles in mammalian reproduction. Physiol Rev. 2019;99:1249–79.

Article  CAS  PubMed  Google Scholar 

Li LA, Chiang EFL, Chen JC, Hsu NC, Chen YJ, Chung BC. Function of steroidogenic factor 1 domains in nuclear localization, transactivation, and interaction with transcription factor TFIIB and c-Jun. Mol Endocrinol. 1999;13:1588–98.

Article  CAS  PubMed  Google Scholar 

Solomon IH, Hager JM, Safi R, McDonnell DP, Redinbo MR, Ortlund EA. Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain positioning is required for receptor activity. J Mol Biol. 2005;354:1091–102.

Article  CAS  PubMed  Google Scholar 

Seacrist CD, Kuenze G, Hoffmann RM, Moeller BE, Burke JE, Meiler J, et al. Integrated structural modeling of full-length LRH-1 reveals inter-domain interactions contribute to receptor structure and function. Structure. 2020;28:830–46.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lu Y, Anderson WR, Zhang H, Feng S, Pick L. Functional conservation of drosophila FTZ-F1 and its mammalian homologs suggests ligand-independent regulation of NR5A family transcriptional activity. Dev Genes Evol. 2013;223:199–205.

Article  CAS  PubMed  Google Scholar 

Steinmetz AC, Renaud JP, Moras D. Binding of ligands and activation of transcription by nuclear receptors. Annu Rev Biophys Biomol Struct. 2001;30:329–59.

Article  CAS  PubMed  Google Scholar 

Sablin EP, Krylova IN, Fletterick RJ, Ingraham HA. Structural basis for ligand-independent activation of the orphan nuclear receptor LRH-1. Mol Cell. 2003;11:1575–85.

Article  CAS  PubMed  Google Scholar 

Nagy L, Schwabe JW. Mechanism of the nuclear receptor molecular switch. Trends Biochem Sci. 2004;29:317–24.

Article  CAS  PubMed  Google Scholar 

Busby S, Nuhant P, Cameron M, Mercer BA, Hodder P, Roush WR, et al. Discovery of inverse agonists for the liver receptor homologue-1 (LRH1; NR5A2). Probe reports from the NIH molecular libraries program. Bethesda (MD): National Center for Biotechnology Information (US); 2010.

Google Scholar 

Forman BM. Are those phospholipids in your pocket? Cell Metab. 2005;1:153–55.

Article  CAS  PubMed  Google Scholar 

Xu D, Jiang X, Wang Y, Song S. Liver receptor homolog-1 regulates apoptosis of bovineovarian granulosa cells by progestogen receptor signaling pathway. Animals. 2022;12:1213.

Article  PubMed  PubMed Central  Google Scholar 

Mays SG, Okafor CD, Whitby RJ, Goswami D, Stec J, Flynn AR, et al. Crystal structures of the nuclear receptor, liver receptor homolog 1, bound to synthetic agonists. J Biol Chem. 2016;291:25281–91.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu X, Zhang Y, Xu Y. Discovery of the first low nanomolar liver receptor homolog-1 (LRH-1) agonist. J Med Chem. 2019;62:11019–21.

Article  CAS  PubMed  Google Scholar 

Cornelison JL, Cato ML, Johnson AM, D’Agostino EH, Melchers D, Patel AB, et al. Development of a new class of liver receptor homolog-1 (LRH-1) agonists by photoredox conjugate addition. Bioorg Med Chem Lett. 2020;30:127293.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cato ML, D’Agostino EH, Spurlin RM, Flynn AR, Cornelison JL, Johnson AM, et al. Comparison of activity, structure, and dynamics of SF-1 and LRH-1 complexed with small molecule modulators. J Biol Chem. 2023;299:104921.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cato ML, Cornelison JL, Spurlin RM, Courouble VV, Patel AB, Flynn AR, et al. Differential modulation of nuclear receptor LRH-1 through targeting buried and surface regions of the binding pocket. J Med Chem. 2022;65:6888–902.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mays SG, Hercules D, Ortlund EA, Okafor CD. The nuclear receptor LRH-1 discriminates between ligands using distinct allosteric signaling circuits. Protein Sci. 2023;32:e4754.

Article  CAS  PubMed  Google Scholar 

Lazarus KA, Wijayakumara D, Chand AL, Simpson ER, Clyne CD. Therapeutic potential of liver receptor homolog-1 modulators. J Steroid Biochem Mol Biol. 2012;130:138–46.

Article  CAS  PubMed  Google Scholar 

Lonard DM, O’malley BW. Nuclear receptor coregulators: judges, juries, and executioners of cellular regulation. Mol Cell. 2007;27:691–700.

Article  CAS  PubMed  Google Scholar 

Zhao H, Li Z, Cooney AJ, Lan ZJ. Orphan nuclear receptor function in the ovary. Front Biosci. 2007;12:3398–405.

Article  CAS  PubMed  Google Scholar 

Suzuki T, Kasahara M, Yoshioka H, Morohashi K, Umesono K. LXXLL-related motifs in Dax-1 have target specificity for the orphan nuclear receptors Ad4BP/SF-1 and LRH-1. Mol Cell Biol. 2003;23:238–49.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yazawa T, Inaoka Y, Okada R, Mizutani T, Yamazaki Y, Usami Y, et al. PPAR-gamma coactivator-1alpha regulates progesterone production in ovarian granulosa cells with SF-1 and LRH-1. Mol Endocrinol. 2010;24:485–96.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Darimont BD, Wagner RL, Apriletti JW, Stallcup MR, Kushner PJ, Baxter JD, et al. Structure and specificity of nuclear receptor-coactivator interactions. Genes Dev. 1998;12:3343–56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stein S, Schoonjans K. Molecular basis for the regulation of the nuclear receptor LRH-1. Curr Opin Cell Biol. 2015;33:26–34.

Article