Molecular aspects of steroidogenic factor 1 (SF-1)

Høivik, Erling A.; Lewis, Aurélia E.; Aumo, Linda; Bakke, Marit

doi:10.1016/j.mce.2009.07.003

Cited by 139 publications

(123 citation statements)

References 200 publications

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“…Therefore, the two nuclear receptors seem to regulate most glycolytic genes by binding to the same genetic loci. However, considering that Ad4BP/SF-1 is expressed only in endocrine tissues, for example, the adrenal cortex and gonads 3,10 , whereas ERRa is expressed in a broad range of tissues 48 , the contribution of these two nuclear receptors to glycolytic gene regulation likely varies among tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Ad4BP/SF-1 (NR5A1), a member of the nuclear receptor superfamily, is expressed specifically in the steroidogenic adrenal cortex and gonads [1][2][3][4][5] . This protein was originally identified as a transcription factor that regulated the steroidogenic CYP11A1 and CYP11B1 genes 6 ; subsequent studies eventually demonstrated that all steroidogenic genes are targets of Ad4BP/SF-1 (refs 7,8).…”

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confidence: 99%

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Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1

et al. 2014

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Genetic deficiencies in transcription factors can lead to the loss of certain types of cells and tissue. The steroidogenic tissue-specific nuclear receptor Ad4BP/SF-1 (NR5A1) is one such gene, because mice in which this gene is disrupted fail to develop the adrenal gland and gonads. However, the specific role of Ad4BP/SF-1 in these biological events remains unclear. Here we use chromatin immunoprecipitation sequencing to show that nearly all genes in the glycolytic pathway are regulated by Ad4BP/SF-1. Suppression of Ad4BP/SF-1 by small interfering RNA reduces production of the energy carriers ATP and nicotinamide adenine dinucleotide phosphate, as well as lowers expression of genes involved in glucose metabolism. Together, these observations may explain tissue dysgenesis as a result of Ad4BP/SF-1 gene disruption in vivo. Considering the function of estrogen-related receptor a, the present study raises the possibility that certain types of nuclear receptors regulate sets of genes involved in metabolic pathways to generate energy carriers.

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Section: Discussionmentioning

confidence: 99%

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Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1

et al. 2014

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“…SF-1, a member of the nuclear receptor superfamily that was initially identified by its capacity to interact with and activate the promoters of steroidogenic enzymes, has emerged as an essential regulator in the mechanisms underlying sex determination, adrenal and gonadal development, reproductive function, and steroidogenesis (Parker et al, 2002;Val et al, 2003;Hoivik et al, 2010). A recent study showed that atrazine upregulates Cyp19a1 gene transcription and alters the sex ratio in zebrafish under environmental conditions, and that the effects on Cyp19a1 are mediated by regulation of downstream SF-1 receptors (Suzawa and Ingraham, 2008).…”

Section: Discussionmentioning

confidence: 99%

Chronic exposure to environmental levels of tribromophenol impairs zebrafish reproduction

Deng

Liu

et al. 2010

Toxicology and Applied Pharmacology

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“…Mutational analysis revealed a heterozygous p.Ala154Thr (c.460 GOA) mutation which lies in hinge region in exon 4. The hinge region is important for transcriptional capacity of SF1 as it contains a phosphorylation site and a synergy control motif with sumoylation sites and hence is predicted to reduce the transcriptional capacity of the protein (24). Both the nucleotide and the amino acid in this position are conserved in human, chimp and rhesus but not in other species (Fig.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Analysis of the gene coding for steroidogenic factor 1 (SF1, NR5A1) in a cohort of 50 Egyptian patients with 46,XY disorders of sex development

Tantawy

Mazen

Soliman

et al. 2014

European Journal of Endocrinology

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Objective: Steroidogenic factor 1 (SF1, NR5A1) is a key transcriptional regulator of genes involved in the hypothalamicpituitary-gonadal axis. Recently, SF1 mutations were found to be a frequent cause of 46,XY disorders of sex development (DSD) in humans. We investigate the frequency of NR5A1 mutations in an Egyptian cohort of XY DSD. Design: Clinical assessment, endocrine evaluation and genetic analysis of 50 Egyptian XY DSD patients (without adrenal insufficiency) with a wide phenotypic spectrum. Methods: Molecular analysis of NR5A1 gene by direct sequencing followed by in vitro functional analysis of the two novel missense mutations detected. Results: Three novel heterozygous mutations of the coding region in patients with hypospadias were detected. p.Glu121AlafsX25 results in severely truncated protein, p.Arg62Cys lies in DNA-binding zinc finger, whereas p.Ala154Thr lies in the hinge region of SF1 protein. Transactivation assays using reporter constructs carrying promoters of anti-Mü llerian hormone (AMH), CYP11A1 and TESCO core enhancer of Sox9 showed that p.Ala154Thr and p.Arg62Cys mutations result in aberrant biological activity of NR5A1. A total of 17 patients (34%) harboured the p.Gly146Ala polymorphism. Conclusion: We identified two novel NR5A1 mutations showing impaired function in 23 Egyptian XY DSD patients with hypospadias (8.5%). This is the first study searching for NR5A1 mutations in oriental patients from the Middle East and Arab region with XY DSD and no adrenal insufficiency, revealing a frequency similar to that in European patients (6.5-15%). We recommend screening of NR5A1 in patients with hypospadias and gonadal dysgenesis. Yearly follow-ups of gonadal function and early cryoconservation of sperms should be performed in XY DSD patients with NR5A1 mutations given the risk of future fertility problems due to early gonadal failure.

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Molecular aspects of steroidogenic factor 1 (SF-1)

Cited by 139 publications

References 200 publications

Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1

Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1

Chronic exposure to environmental levels of tribromophenol impairs zebrafish reproduction

Analysis of the gene coding for steroidogenic factor 1 (SF1, NR5A1) in a cohort of 50 Egyptian patients with 46,XY disorders of sex development

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