Steroidogenic Factor-1 form and function: From phospholipids to physiology.

Steroidogenic Factor-1 (SF-1, NR5A1) is a member of the nuclear receptor superfamily of ligand-regulated transcription factors, consisting of a DNA-binding domain (DBD) connected to a transcriptional regulatory ligand binding domain (LBD) via an unstructured hinge domain. SF-1 is a master regulator of development and adult function along the hypothalamic pituitary adrenal and gonadal axes, with strong pathophysiological association with endometriosis and adrenocortical carcinoma. SF-1 was shown to bind and be regulated by phospholipids, one of the most interesting aspects of SF-1 regulation is the manner in which SF-1 interacts with phospholipids: SF-1 buries the phospholipid acyl chains deep in the hydrophobic core of the SF-1 protein, while the lipid headgroups remain solvent-exposed on the exterior of the SF-1 protein surface. Here, we have reviewed several aspects of SF-1 structure, function and physiology, touching on other transcription factors that help regulate SF-1 target genes, non-canonical functions of SF-1, the DNA-binding properties of SF-1, the use of mass spectrometry to identify lipids that associate with SF-1, how protein phosphorylation regulates SF-1 and the structural biology of the phospholipid-ligand binding domain. Together this review summarizes the form and function of Steroidogenic Factor-1 in physiology and in human disease, with particular emphasis on adrenal cancer.

• Publication year

  2023

• Venue

  Advances in Biological Regulation

• Publication date

  2023-09-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.jbior.2023.100991PMID 37802761PMCID PMC10922105
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Comparison of activity, structure, and dynamics of SF-1 and LRH-1 complexed with small molecule modulators

  2023cited by this paper
• MicroRNA-92a-3p Inhibits Cell Proliferation and Invasion by Regulating the Transcription Factor 21/Steroidogenic Factor 1 Axis in Endometriosis

  2023cited by this paper
• Nuclear Phosphoinositides as Key Determinants of Nuclear Functions

  2023cited by this paper
• Steroidogenic factor 1 (SF-1; Nr5a1) regulates the formation of the ovarian reserve

  2023cited by this paper
• Genetic reanalysis of patients with a difference of sex development carrying the NR5A1/SF-1 variant p.Gly146Ala has discovered other likely disease-causing variations

  2023cited by this paper
• Inhibition of high-fat diet-induced inflammatory responses in adipose tissue by SF1-expressing neurons of the ventromedial hypothalamus.

  2023cited by this paper
• Case Report: Longitudinal follow-up and testicular sperm extraction in a patient with a pathogenic NR5A1 (SF-1) frameshift variant: p.(Phe70Serfs*5)

  2023cited by this paper
• Steroidogenic Factor 1, a Goldilocks Transcription Factor from Adrenocortical Organogenesis to Malignancy

  2023cited by this paper
• Comprehensive Characterization of the Regulatory Landscape of Adrenocortical Carcinoma: Novel Transcription Factors and Targets Associated with Prognosis

  2022cited by this paper
• Steroidogenic factor 1 regulation of the hypothalamic-pituitary-ovarian axis of adult female mice.

  2022cited by this paper
• A Systematic Review of Published Clinical Trials in the Systemic Treatment of Adrenocortical Carcinoma: An Initiative Led on Behalf of the Global Society of Rare Genitourinary Tumors.

  2022cited by this paper
• New Insights of SF1 Neurons in Hypothalamic Regulation of Obesity and Diabetes

  2021cited by this paper
• The acyl chains of phosphoinositide PIP3 alter the structure and function of nuclear receptor steroidogenic factor-1

  2021cited by this paper
• Ventromedial Nucleus of the Hypothalamus Neurons Under the Magnifying Glass

  2021cited by this paper
• Enantiomer-specific activities of an LRH-1 and SF-1 dual agonist

  2020cited by this paper
• Integrated Structural Modeling of Full-Length LRH-1 Reveals Inter-domain Interactions Contribute to Receptor Structure and Function.

  2020cited by this paper
• Nuclear phosphoinositides and phase separation: Important players in nuclear compartmentalization.

  2019cited by this paper
• The Orphan Nuclear Receptors Steroidogenic Factor-1 and Liver Receptor Homolog-1: Structure, Regulation, and Essential Roles in Mammalian Reproduction.

  2019cited by this paper
• In cases of familial primary ovarian insufficiency and disorders of gonadal development, consider NR5A1/SF-1 sequence variants.

  2019cited by this paper
• How is the acyl chain composition of phosphoinositides created and does it matter?

  2019cited by this paper
• Next-Generation Sequencing Reveals Novel Genetic Variants (SRY, DMRT1, NR5A1, DHH, DHX37) in Adults With 46,XY DSD

  2019cited by this paper
• The importance of the multiplex ligation-dependent probe amplification in the identification of a novel two-exon deletion of the NR5A1 gene in a patient with 46,XY differences of sex development

  2019cited by this paper
• Structural basis of NR4A1 bound to the human pituitary proopiomelanocortin gene promoter.

  2019cited by this paper
• Signaling through non-membrane nuclear phosphoinositide binding proteins in human health and disease

  2018cited by this paper
• Non-genomic effects of nuclear receptors: insights from the anucleate platelet

  2018cited by this paper
• Nuclear phosphoinositide regulation of chromatin

  2018cited by this paper
• The nuclear receptor superfamily: A structural perspective

  2018cited by this paper
• Phospholipid regulation of the nuclear receptor superfamily.

  2017cited by this paper
• Neuronal control of peripheral insulin sensitivity and glucose metabolism

  2017cited by this paper
• Activation of SF1 Neurons in the Ventromedial Hypothalamus by DREADD Technology Increases Insulin Sensitivity in Peripheral Tissues

  2017cited by this paper
• SF-1 expression in the hypothalamus is required for beneficial metabolic effects of exercise

  2016cited by this paper
• A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF), and Liver Receptor Homolog-1 (LRH-1).

  2016cited by this paper
• Endometrial Expression of Steroidogenic Factor 1 Promotes Cystic Glandular Morphogenesis.

  2016cited by this paper
• The signaling phospholipid PIP3 creates a new interaction surface on the nuclear receptor SF-1

  2014cited by this paper
• NR5A1 prevents centriole splitting by inhibiting centrosomal DNA-PK activation and β-catenin accumulation

  2014cited by this paper
• A new approach to measuring phosphoinositides in cells by mass spectrometry.

  2014cited by this paper
• Phosphoinositides: tiny lipids with giant impact on cell regulation.

  2013cited by this paper
• Nuclear phosphoinositides and their impact on nuclear functions

  2013cited by this paper
• Revisiting the Ventral Medial Nucleus of the Hypothalamus: The Roles of SF-1 Neurons in Energy Homeostasis

  2013cited by this paper
• Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation

  2013cited by this paper
• Ligand structural motifs can decouple glucocorticoid receptor transcriptional activation from target promoter occupancy.

  2012cited by this paper
• FOXO1 in the ventromedial hypothalamus regulates energy balance.

  2012cited by this paper
• Knockdown of SF-1 and RNF31 Affects Components of Steroidogenesis, TGFβ, and Wnt/β-catenin Signaling in Adrenocortical Carcinoma Cells

  2012cited by this paper
• Steroidogenic Factor 1 (NR5A1) Maintains Centrosome Homeostasis in Steroidogenic Cells by Restricting Centrosomal DNA-Dependent Protein Kinase Activation

  2012cited by this paper
• Direct Modification and Activation of a Nuclear Receptor–PIP2 Complex by the Inositol Lipid Kinase IPMK

  2012cited by this paper
• Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus

  2011cited by this paper
• The steroidogenic factor-1 protein is not expressed in various forms of endometriosis but is strongly present in ovarian cortical or medullary mesenchymatous cells adjacent to endometriotic foci.

  2011cited by this paper
• Small molecule agonists of the orphan nuclear receptors steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homologue-1 (LRH-1, NR5A2).

  2011cited by this paper
• Eliminating SF-1 (NR5A1) sumoylation in vivo results in ectopic hedgehog signaling and disruption of endocrine development.

  2011cited by this paper
• Central insulin and leptin-mediated autonomic control of glucose homeostasis.

  2011cited by this paper
• High-fat Feeding Promotes Obesity via Insulin Receptor/PI3k-Dependent Inhibition of SF-1 VMH Neurons

  2011cited by this paper
• Steroidogenic Factor 1 (NR5A1) resides in centrosomes and maintains genomic stability by controlling centrosome homeostasis

  2011cited by this paper
• The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.

  2011cited by this paper
• Human steroidogenic factor-1 (hSF-1) regulates progesterone biosynthesis and growth of ovarian surface epithelial cancer cells.

  2010cited by this paper
• Nuclear phosphoinositides: a signaling enigma wrapped in a compartmental conundrum.

  2010cited by this paper
• Prostaglandin E2 via steroidogenic factor-1 coordinately regulates transcription of steroidogenic genes necessary for estrogen synthesis in endometriosis.

  2009cited by this paper
• Inhibition of adrenocortical carcinoma cell proliferation by steroidogenic factor-1 inverse agonists.

  2009cited by this paper
• Regulation of aldosterone and cortisol production by the transcriptional repressor neuron restrictive silencer factor.

  2009cited by this paper
• A Mechanism Linking Extra Centrosomes to Chromosomal Instability

  2009cited by this paper
• Cep76, a centrosomal protein that specifically restrains centriole reduplication.

  2009cited by this paper
• Structure of SF-1 bound by different phospholipids: evidence for regulatory ligands.

  2009cited by this paper
• Centriole separation in DNA damage‐induced centrosome amplification

  2009cited by this paper
• Steroidogenic Factor-1 (SF-1, Ad4BP, NR5A1) and Disorders of Testis Development

  2008cited by this paper
• Upstream stimulatory factor-2 regulates steroidogenic factor-1 expression in endometriosis.

  2008cited by this paper
• Phosphorylation of steroidogenic factor 1 is mediated by cyclin-dependent kinase 7.

  2008cited by this paper
• Dido disruption leads to centrosome amplification and mitotic checkpoint defects compromising chromosome stability

  2007cited by this paper
• Increased steroidogenic factor-1 dosage triggers adrenocortical cell proliferation and cancer.

  2007cited by this paper
• Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemia.

  2007cited by this paper
• Steroidogenic factor-1 is a sphingolipid binding protein.

  2007cited by this paper
• Oncogenes and tumour suppressors take on centrosomes

  2007cited by this paper
• Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5' CpG island in endometriosis.

  2007cited by this paper
• Preventing the degradation of mps1 at centrosomes is sufficient to cause centrosome reduplication in human cells.

  2007cited by this paper
• Sphingosine regulates the transcription of CYP17 by binding to steroidogenic factor-1.

  2006cited by this paper
• Sequence-specific deoxyribonucleic acid (DNA) recognition by steroidogenic factor 1: a helix at the carboxy terminus of the DNA binding domain is necessary for complex stability.

  2006cited by this paper
• Crystallographic identification and functional characterization of phospholipids as ligands for the orphan nuclear receptor steroidogenic factor-1.

  2005cited by this paper
• The crystal structures of human steroidogenic factor-1 and liver receptor homologue-1.

  2005cited by this paper
• Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1.

  2005cited by this paper
• Transcription factors GATA-6, SF-1, and cell proliferation in human adrenocortical tumors.

  2005cited by this paper
• Centrosome control of the cell cycle Centrosome control of the cell cycle Centrosome control of the cell cycle Centrosome control of the cell cycle

  2005cited by this paper
• Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain positioning is required for receptor activity.

  2005cited by this paper
• Are those phospholipids in your pocket?

  2005cited by this paper
• Differential requirement for steroidogenic factor-1 gene dosage in adrenal development versus endocrine function.

  2004cited by this paper
• Monomeric complex of human orphan estrogen related receptor-2 with DNA: a pseudo-dimer interface mediates extended half-site recognition.

  2003cited by this paper
• Activation of cAMP-dependent protein kinase increases the protein level of steroidogenic factor-1.

  2002cited by this paper
• Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity.

  2002cited by this paper
• Activation of cAMP-Dependent Protein Kinase Increases the Protein Level of Steroidogenic Factor-1.

  2002cited by this paper
• Centrosome amplification and the development of cancer

  2002cited by this paper
• Phosphorylation and Intramolecular Stabilization of the Ligand Binding Domain in the Nuclear Receptor Steroidogenic Factor 1

  2002cited by this paper
• CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells.

  2002cited by this paper
• Steroidogenic factor 1 (SF1) is essential for pituitary gonadotrope function.

  2001cited by this paper
• Effects of mutating different steroidogenic factor-1 protein regions on gene regulation

  2001cited by this paper
• Re-evaluating centrosome function

  2001cited by this paper
• Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors.

  2000cited by this paper
• Mannheim classification of nongenomically initiated (rapid) steroid action(s).

  2000cited by this paper
• Apparently normal ovarian differentiation in a prepubertal girl with transcriptionally inactive steroidogenic factor 1 (NR5A1/SF-1) and adrenocortical insufficiency.

  2000cited by this paper
• Asymmetry in the PPARγ/RXRα Crystal Structure Reveals the Molecular Basis of Heterodimerization among Nuclear Receptors

  2000cited by this paper
• Gene Dosage Effects of Steroidogenic Factor 1 (SF-1) in Adrenal Development and the Stress

  2000cited by this paper
• Haploinsufficiency of steroidogenic factor-1 in mice disrupts adrenal development leading to an impaired stress response.

  2000cited by this paper
• Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication.

  2000cited by this paper
• A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans

  1999cited by this paper

• Methylation status of PAX1 and SF-1: implications for diagnosis and prognosis in endometrial cancer.

  2025cites this paper
• Close relationship, similar phenotype of GATA4 and NR5A1 mutations: gonadal dysgenesis and puberty development

  2025cites this paper
• Diagnosis and grading of adrenal cortical carcinoma

  2025cites this paper
• Potential endogenous lipid ligands for the nuclear receptor transcription factor Steroidogenic Factor-1

  2025cites this paper
• Phosphoinositide signaling in the nucleus: Impacts on chromatin and transcription regulation

  2024cites this paper
• Characterization of sf-1 expression and identification its role in regulating sexual development of golden pompano (Trachinotus blochii)

  2024cites this paper