Cited by 269Adrenal Hormones and DisordersSexual Differentiation and DisordersEstrogen and related hormone effects

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Minireview: Steroidogenic Factor 1: Its Roles in Differentiation, Development, and Disease

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Schimmer, Bernard P., White, Perrin C.·2010·Molecular Endocrinology

DOI 10.1210/me.2009-0519PMC PMC5417463

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Abstract

The orphan nuclear receptor steroidogenic factor 1 (SF-1, also called Ad4BP, encoded by the NR5A1 gene) is an essential regulator of endocrine development and function. Initially identified as a tissue-specific transcriptional regulator of cytochrome P450 steroid hydroxylases, studies of both global and tissue-specific knockout mice have demonstrated that SF-1 is required for the development of the adrenal glands, gonads, and ventromedial hypothalamus and for the proper functioning of pituitary gonadotropes. Many genes are transcriptionally regulated by SF-1, and many proteins, in turn, interact with SF-1 and modulate its activity. Whereas mice with heterozygous mutations that disrupt SF-1 function have only subtle abnormalities, humans with heterozygous SF-1 mutations can present with XY sex reversal (i.e. testicular failure), ovarian failure, and occasionally adrenal insufficiency; dysregulation of SF-1 has been linked to diseases such as endometriosis and adrenocortical carcinoma. The current state of knowledge of this important transcription factor will be reviewed with a particular emphasis on the pioneering work on SF-1 by the late Keith Parker.

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Reciprocal Regulation of a Glucocorticoid Receptor-Steroidogenic Factor-1 Transcription Complex on the Dax-1 Promoter by Glucocorticoids and Adrenocorticotropic Hormone in the Adrenal Cortex
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Small Ubiquitin-Like Modifier 1 (SUMO-1) Modification of the Synergy Control Motif of Ad4 Binding Protein/Steroidogenic Factor 1 (Ad4BP/SF-1) Regulates Synergistic Transcription between Ad4BP/SF-1 and Sox9
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Steroidogenic Factor 1 Messenger Ribonucleic Acid Expression in Steroidogenic and Nonsteroidogenic Human Tissues: Northern Blot and in Situ Hybridization Studies
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Phosphorylation and Intramolecular Stabilization of the Ligand Binding Domain in the Nuclear Receptor Steroidogenic Factor 1
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SUMO modification of repression domains modulates function of nuclear receptor 5A1 (steroidogenic factor-1)
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A Binding Site for Steroidogenic Factor-1 is Part of a Complex Enhancer that Mediates Expression of the Murine Gonadotropin-Releasing Hormone Receptor Gene1
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SF-1 overexpression in childhood adrenocortical tumours
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The Activation Function-2 Hexamer of Steroidogenic Factor-1 Is Required, but Not Sufficient for Potentiation by SRC-1
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The Role of Human MBF1 as a Transcriptional Coactivator
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Convergence of Wnt Signaling and Steroidogenic Factor-1 (SF-1) on Transcription of the Rat Inhibin α Gene
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Mouse Polycomb M33 is required for splenic vascular and adrenal gland formation through regulating Ad4BP/SF1 expression
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Transcription of the Leydig Insulin-Like Gene Is Mediated by Steroidogenic Factor-1
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Identification of Small Molecule Agonists of the Orphan Nuclear Receptors Liver Receptor Homolog-1 and Steroidogenic Factor-1
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Steroidogenic Factor-1 Interacts with a Gonadotrope-Specific Element within the First Exon of the Human Gonadotropin-Releasing Hormone Receptor Gene to Mediate Gonadotrope-Specific Expression
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Hormonal Regulation of Messenger Ribonucleic Acid Expression for Steroidogenic Factor-1, Steroidogenic Acute Regulatory Protein, and Cytochrome P450 Side-Chain Cleavage in Bovine Luteal Cells
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Acetylation of Steroidogenic Factor 1 Protein Regulates Its Transcriptional Activity and Recruits the Coactivator GCN5
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Function of Steroidogenic Factor 1 Domains in Nuclear Localization, Transactivation, and Interaction with Transcription Factor TFIIB and c-Jun
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Structure of SF-1 Bound by Different Phospholipids: Evidence for Regulatory Ligands
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The Role of the Orphan Nuclear Receptor, Liver Receptor Homologue-1, in the Regulation of Human Corpus Luteum 3β-Hydroxysteroid Dehydrogenase Type II
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Diminished hypothalamic bdnf expression and impaired VMH function are associated with reduced SF‐1 gene dosage
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Central Nervous System-Specific Knockout of Steroidogenic Factor 1 Results in Increased Anxiety-Like Behavior
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SF-1 (Nuclear Receptor 5A1) Activity Is Activated by Cyclic AMP via p300-Mediated Recruitment to Active Foci, Acetylation, and Increased DNA Binding
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The DEAD Box Protein DP103 Is a Regulator of Steroidogenic Factor-1
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Expression of murine 21-hydroxylase in mouse adrenal glands and in transfected Y1 adrenocortical tumor cells
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Adipose Tissue-Derived and Bone Marrow-Derived Mesenchymal Cells Develop into Different Lineage of Steroidogenic Cells by Forced Expression of Steroidogenic Factor 1
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Oxysterol Regulation of Steroidogenic Acute Regulatory Protein Gene Expression
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Adrenocorticotropic Hormone-Mediated Signaling Cascades Coordinate a Cyclic Pattern of Steroidogenic Factor 1-Dependent Transcriptional Activation
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AR Suppresses Transcription of the LH Subunit by Interacting with Steroidogenic Factor-1
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25-Hydroxycholesterol Is Not a Ligand for the Orphan Nuclear Receptor Steroidogenic Factor-1 (SF-1)
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Characterization of the Promoter of SF-1, an Orphan Nuclear Receptor Required for Adrenal and Gonadal Development
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Molecular mechanism for cooperation between Sp1 and steroidogenic factor-1 (SF-1) to regulate bovine CYP11A gene expression
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Expression of MIS in the Testis Is Downregulated by Tumor Necrosis Factor Alpha through the Negative Regulation of SF-1 Transactivation by NF-κB
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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
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Role of Steroidogenic-Factor 1 in Basal and 3′,5′-Cyclic Adenosine Monophosphate-Mediated Regulation of Cytochrome P450 Side-Chain Cleavage Enzyme in the Mouse1
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Adrenocorticotropin-Dependent Changes in SF-1/DAX-1 Ratio Influence Steroidogenic Genes Expression in a Novel Model of Glucocorticoid-Producing Adrenocortical Cell Lines Derived from Targeted Tumorigenesis
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Development of a Transgenic Green Fluorescent Protein Lineage Marker for Steroidogenic Factor 1
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The Orphan Receptors NGFI-B and Steroidogenic Factor 1 Establish Monomer Binding as a Third Paradigm of Nuclear Receptor-DNA Interaction
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SF‐1/Ad4BP transforms primary long‐term cultured bone marrow cells into ACTH‐responsive steroidogenic cells
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Synergistic Cooperation between the β-Catenin Signaling Pathway and Steroidogenic Factor 1 in the Activation of the Mullerian Inhibiting Substance Type II Receptor
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Transgenic Expression ofAd4BP/SF-1in Fetal Adrenal Progenitor Cells Leads to Ectopic Adrenal Formation
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The Basic Helix-Loop-Helix, Leucine Zipper Transcription Factor, USF (Upstream Stimulatory Factor), Is a Key Regulator of SF-1 (Steroidogenic Factor-1) Gene Expression in Pituitary Gonadotrope and Steroidogenic Cells
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Genes essential for early events in gonadal development
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Nuclear Factor Y and Steroidogenic Factor 1 Physically and Functionally Interact to Contribute to Cell-Specific Expression of the Mouse Follicle-Stimulating Hormone-β Gene
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Steroidogenic Factor-1 Mediates Cyclic 3',5'-Adenosine Monophosphate Regulation of the High Density Lipoprotein Receptor
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SUMOylation Inhibits SF-1 Activity by Reducing CDK7-Mediated Serine 203 Phosphorylation
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An enhancer element and a functional cyclic AMP-dependent protein kinase are required for expression of adrenocortical 21-hydroxylase.
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Pod-1/Capsulin shows a sex- and stage-dependent expression pattern in the mouse gonad development and represses expression of Ad4BP/SF-1
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The Nuclear Receptor Coactivators p300/CBP/Cointegrator-Associated Protein (p/CIP) and Transcription Intermediary Factor 2 (TIF2) Differentially Regulate PKA-Stimulated Transcriptional Activity of Steroidogenic Factor 1
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Expression of Steroidogenic Factor 1 in the Testis Requires an E Box and CCAAT Box in its Promoter Proximal Region1
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Decreased Recognition of SUMO-Sensitive Target Genes following Modification of SF-1 (NR5A1)
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Protein Kinase A Potentiates Adrenal 4 Binding Protein/Steroidogenic Factor 1 Transactivation by Reintegrating the Subcellular Dynamic Interactions of the Nuclear Receptor with Its Cofactors, General Control Nonderepressed-5/Transformation/ Transcription Domain-Associated Protein, and Suppressor, Dosage-Sensitive Sex Reversal-1: a Laser Confocal Imaging Study in Living KGN Cells
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Steroidogenic factor 1/adrenal 4 binding protein transforms human bone marrow mesenchymal cells into steroidogenic cells
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SF-1 (Steroidogenic Factor-1), C/EBP (CCAAT/Enhancer Binding Protein), and Ubiquitous Transcription Factors NF1 (Nuclear Factor 1) and Sp1 (Selective Promoter Factor 1) Are Required for Regulation of the Mouse Aldose Reductase-Like Gene (AKR1B7) Expression in Adrenocortical Cells
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The transcriptional regulating protein of 132 kDa (TReP-132) enhances P450scc gene transcription through interaction with steroidogenic factor-1 in human adrenal cells
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Cyclic AMP-Stimulated Interaction between Steroidogenic Factor 1 and Diacylglycerol Kinase θ Facilitates Induction of CYP17
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Sexually dimorphic expression of Dax‐1 in the adrenal cortex
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Activation of cAMP-Dependent Protein Kinase Increases the Protein Level of Steroidogenic Factor-1
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RIP 140 Modulates Transcription of the Steroidogenic Acute Regulatory Protein Gene through Interactions with Both SF-1 and DAX-1
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Characterization of a regulatory region of the steroid 21-hydroxylase gene.
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Function and distribution of a steroidogenic cell-specific transcription factor, Ad4BP
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Hedgehog Signaling: Is Smo a G Protein-Coupled Receptor?
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Phosphorylation of Steroidogenic Factor 1 Is Mediated by Cyclin-Dependent Kinase 7
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Genes essential for early events in gonadal development
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Central nervous system-specific knockout of steroidogenic factor 1
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Adrenocortical and Gonadal Expression of the Mammalian Ftz-F1 Gene Encoding Ad4BP/SF-1 Is Independent of Pituitary Control
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Ventromedial Hypothalamic Nucleus-Specific Enhancer of Ad4BP/SF-1 Gene
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Pituitary Homeobox 2 Regulates Adrenal4 Binding Protein/Steroidogenic Factor-1 Gene Transcription in the Pituitary Gonadotrope through Interaction with the Intronic Enhancer
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Deoxyribonucleic Acid Methylation Controls Cell Type-Specific Expression of Steroidogenic Factor 1
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Inhibition of steroidogenesis in Leydig cells by Müllerian-inhibiting substance
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Authors: Schimmer, B. P., & White, P. C.
Affiliations: University of Toronto (CA)
ORCID: White, Perrin C.
Venue: Molecular Endocrinology
Publisher: The Endocrine Society
Published: 2010-07
Volume: 24
Issue: 7
Pages: 1322-1337
ISSN: 0888-8809 (ISSN-L)
1944-9917
DOI: 10.1210/me.2009-0519
PMC: PMC5417463
OpenAlex: W2039590485
Cited by: 268
References: 176
Citations by year: 2026: 13 · 2025: 14 · 2024: 15 · 2023: 15 · 2022: 12 · 2021: 14 · 2020: 9 · 2019: 14 · 2018: 15 · 2017: 12 · 2016: 14 · 2015: 29 · 2014: 18 · 2013: 17 · 2012: 27
FWCI: 3.31
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Molecular Endocrinology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Institutes of Health Research (MOP-64325)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Keywords: steroidogenic factor 1, orphan nuclear receptor, transcriptional regulation, adrenal development, gonad development, ventromedial hypothalamus, gonadotrophs, XY sex reversal, ovarian failure, adrenal insufficiency, endometriosis, adrenocortical carcinoma, heterozygous mutation
MeSH terms: Animals, Disease, Humans, Hypothalamus, Mutation, Pituitary Gland, Protein Binding, Mice, Knockout, Mice, Steroidogenic Factor 1

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