Version 1
: Received: 11 August 2024 / Approved: 12 August 2024 / Online: 14 August 2024 (09:17:30 CEST)
How to cite:
Naamneh Elzenaty, R.; Kouri, C.; Martinez de Lapiscina, I.; Sauter, K. S.; Moreno, F.; Camats Tarruella, N.; Flück, C. E. NR5A1/SF-1 Collaborates with Inhibin α and the Androgen Receptor to Reveal a Complex DSD Phenotype. Preprints2024, 2024080883. https://doi.org/10.20944/preprints202408.0883.v1
Naamneh Elzenaty, R.; Kouri, C.; Martinez de Lapiscina, I.; Sauter, K. S.; Moreno, F.; Camats Tarruella, N.; Flück, C. E. NR5A1/SF-1 Collaborates with Inhibin α and the Androgen Receptor to Reveal a Complex DSD Phenotype. Preprints 2024, 2024080883. https://doi.org/10.20944/preprints202408.0883.v1
Naamneh Elzenaty, R.; Kouri, C.; Martinez de Lapiscina, I.; Sauter, K. S.; Moreno, F.; Camats Tarruella, N.; Flück, C. E. NR5A1/SF-1 Collaborates with Inhibin α and the Androgen Receptor to Reveal a Complex DSD Phenotype. Preprints2024, 2024080883. https://doi.org/10.20944/preprints202408.0883.v1
APA Style
Naamneh Elzenaty, R., Kouri, C., Martinez de Lapiscina, I., Sauter, K. S., Moreno, F., Camats Tarruella, N., & Flück, C. E. (2024). NR5A1/SF-1 Collaborates with Inhibin α and the Androgen Receptor to Reveal a Complex DSD Phenotype. Preprints. https://doi.org/10.20944/preprints202408.0883.v1
Chicago/Turabian Style
Naamneh Elzenaty, R., Núria Camats Tarruella and Christa E. Flück. 2024 "NR5A1/SF-1 Collaborates with Inhibin α and the Androgen Receptor to Reveal a Complex DSD Phenotype" Preprints. https://doi.org/10.20944/preprints202408.0883.v1
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 (DSD). Oligogenic inheritance has been suggested as an explanation. However, testing the impact of specific gene variants involved in a network remains difficult. To confirm the hypothesis that NR5A1/SF-1-related DSD follow an oligogenic mode of inheritance, we investigated a constellation of gene variants identified in a 46,XY severely undervirilized individual. 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. Functional testing was conducted 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 ac-tivity. 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 strengthening the hypothesis that the broad phenotype observed in 46,XY DSD individuals may be caused by oligogenic pathogenicity.
Keywords
steroidogenic factor 1 (SF-1/NR5A1); inhibin , androgen receptor; differences of sex development (DSD); 46,XY DSD; hypospadias; oligogenicity
Subject
Biology and Life Sciences, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
