dc.contributor
Institut Català de la Salut
dc.contributor
[Naamneh Elzenaty R, Naamneh Elzenaty C] Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Department of BioMedical Research, University of Bern, Bern, Switzerland. Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. [Martinez de Lapiscina I] Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Department of BioMedical Research, University of Bern, Bern, Switzerland. Biobizkaia Health Research Institute, Cruces University Hospital, University of the Basque, Barakaldo, Spain. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain. Endo-ERN, HV Amsterdam, The Netherlands. [Sauter KS] Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Department of BioMedical Research, University of Bern, Bern, Switzerland. [Moreno F] Department of Pediatrics, Hospital Infantil La Fe, Valencia, Spain. [Camats-Tarruella N] Grup de Recerca de Creixement i Desenvolupament, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Naamneh Elzenaty, Rawda
dc.contributor.author
Sauter, Kay Sara
dc.contributor.author
Moreno Macián, Francisca
dc.contributor.author
Kouri, Chrysanthi
dc.contributor.author
Martinez de LaPiscina Martin, Idoia
dc.contributor.author
Camats Tarruella, Núria
dc.date.accessioned
2025-10-24T08:54:05Z
dc.date.available
2025-10-24T08:54:05Z
dc.date.issued
2024-11-06T12:24:19Z
dc.date.issued
2024-11-06T12:24:19Z
dc.date.issued
2024-09-20
dc.identifier
Naamneh Elzenaty R, Kouri C, Martinez de Lapiscina I, Sauter KS, Moreno F, Camats-Tarruella N, et al. NR5A1/SF-1 Collaborates with Inhibin α and the Androgen Receptor. Int J Mol Sci. 2024 Sep 20;25(18):10109.
dc.identifier
https://hdl.handle.net/11351/12186
dc.identifier
10.3390/ijms251810109
dc.identifier
001326162800001
dc.identifier.uri
http://hdl.handle.net/11351/12186
dc.description.abstract
Androgen receptor; Disorders of sex development; Steroidogenic factor 1
dc.description.abstract
Receptor de andrógenos; Trastornos del desarrollo sexual; Factor esteroidogénico 1
dc.description.abstract
Receptor d'andrògens; Trastorns del desenvolupament sexual; Factor esteroidogènic 1
dc.description.abstract
Steroidogenic factor 1 (SF-1) is a nuclear receptor that regulates steroidogenesis and reproductive development. NR5A1/SF-1 variants are associated with a broad spectrum of phenotypes across individuals with disorders of sex development (DSDs). Oligogenic inheritance has been suggested as an explanation. SF-1 interacts with numerous partners. Here, we investigated a constellation of gene variants identified in a 46,XY severely undervirilized individual carrying an ACMG-categorized 'pathogenic' NR5A1/SF-1 variant in comparison to the healthy carrier father. Candidate genes were revealed by whole exome sequencing, and pathogenicity was predicted by different in silico tools. We found variants in NR1H2 and INHA associated with steroidogenesis, sex development, and reproduction. The identified variants were tested in cell models. Novel SF-1 and NR1H2 binding sites in the AR and INHA gene promoters were found. Transactivation studies showed that wild-type NR5A1/SF-1 regulates INHA and AR gene expression, while the NR5A1/SF-1 variant had decreased transcriptional activity. NR1H2 was found to regulate AR gene transcription; however, the NR1H2 variant showed normal activity. This study expands the NR5A1/SF-1 network of interacting partners, while not solving the exact interplay of different variants that might be involved in revealing the observed DSD phenotype. It also illustrates that understanding complex genetics in DSDs is challenging.
dc.description.abstract
This study was supported by a project grant from the Swiss National Science Foundation (320030-197725). I.M.d.L. is supported by a Postdoctoral Fellowship Grant from the Education Department of the Basque Government (Spain) (POS_2020_1_0034).
dc.format
application/pdf
dc.relation
International Journal of Molecular Sciences;25(18)
dc.relation
https://doi.org/10.3390/ijms251810109
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Diferenciació sexual - Trastorns
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Hormones esteroides - Receptors
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CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Androgen
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CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Steroidogenic Factor 1
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DISEASES::Endocrine System Diseases::Gonadal Disorders::Disorders of Sex Development
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Other subheadings::Other subheadings::Other subheadings::/genetics
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COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::receptores citoplásmicos y nucleares::receptores de esteroides::receptores de andrógenos
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::receptores citoplásmicos y nucleares::factor 1 esteroidogénico
dc.subject
ENFERMEDADES::enfermedades del sistema endocrino::trastornos gonadales::trastornos del desarrollo sexual
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/genética
dc.title
NR5A1/SF-1 Collaborates with Inhibin α and the Androgen Receptor
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
