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Testosterone-induced increase in libido in a patient with a loss-of-function mutation in the AR gene

SUMMARY: Complete androgen-insensitivity syndrome (CAIS), a disorder of sex development (46,XY DSD), is caused primarily by mutations in the androgen receptor (AR). Gonadectomy is recommended due to the increased risk of gonadoblastoma, however, surgical intervention is often followed by loss of lib...

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Autores principales: Marino, Laura, Messina, Andrea, S Acierno, James, Phan-Hug, Franziska, J Niederländer, Nicolas, Santoni, Federico, La Rosa, Stefano, Pitteloud, Nelly
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240814/
https://www.ncbi.nlm.nih.gov/pubmed/34152287
http://dx.doi.org/10.1530/EDM-21-0031
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author Marino, Laura
Messina, Andrea
S Acierno, James
Phan-Hug, Franziska
J Niederländer, Nicolas
Santoni, Federico
La Rosa, Stefano
Pitteloud, Nelly
author_facet Marino, Laura
Messina, Andrea
S Acierno, James
Phan-Hug, Franziska
J Niederländer, Nicolas
Santoni, Federico
La Rosa, Stefano
Pitteloud, Nelly
author_sort Marino, Laura
collection PubMed
description SUMMARY: Complete androgen-insensitivity syndrome (CAIS), a disorder of sex development (46,XY DSD), is caused primarily by mutations in the androgen receptor (AR). Gonadectomy is recommended due to the increased risk of gonadoblastoma, however, surgical intervention is often followed by loss of libido. We present a 26-year-old patient with CAIS who underwent gonadectomy followed by a significant decrease in libido, which was improved with testosterone treatment but not with estradiol. Genetic testing was performed and followed by molecular characterization. We found that this patient carried a previously unidentified start loss mutation in the androgen receptor. This variant resulted in an N-terminal truncated protein with an intact DNA binding domain and was confirmed to be loss-of-function in vitro. This unique CAIS case and detailed functional studies raise intriguing questions regarding the relative roles of testosterone and estrogen in libido, and in particular, the potential non-genomic actions of androgens. LEARNING POINTS: N-terminal truncation of androgen receptor can cause androgen-insensitivity syndrome. Surgical removal of testosterone-producing gonads can result in loss of libido. Libido may be improved with testosterone treatment but not with estradiol in some forms of CAIS. A previously unreported AR mutation – p.Glu2_Met190del (c.2T>C) – is found in a CAIS patient and results in blunted AR transcriptional activity under testosterone treatment.
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spelling pubmed-82408142021-07-01 Testosterone-induced increase in libido in a patient with a loss-of-function mutation in the AR gene Marino, Laura Messina, Andrea S Acierno, James Phan-Hug, Franziska J Niederländer, Nicolas Santoni, Federico La Rosa, Stefano Pitteloud, Nelly Endocrinol Diabetes Metab Case Rep Insight into Disease Pathogenesis or Mechanism of Therapy SUMMARY: Complete androgen-insensitivity syndrome (CAIS), a disorder of sex development (46,XY DSD), is caused primarily by mutations in the androgen receptor (AR). Gonadectomy is recommended due to the increased risk of gonadoblastoma, however, surgical intervention is often followed by loss of libido. We present a 26-year-old patient with CAIS who underwent gonadectomy followed by a significant decrease in libido, which was improved with testosterone treatment but not with estradiol. Genetic testing was performed and followed by molecular characterization. We found that this patient carried a previously unidentified start loss mutation in the androgen receptor. This variant resulted in an N-terminal truncated protein with an intact DNA binding domain and was confirmed to be loss-of-function in vitro. This unique CAIS case and detailed functional studies raise intriguing questions regarding the relative roles of testosterone and estrogen in libido, and in particular, the potential non-genomic actions of androgens. LEARNING POINTS: N-terminal truncation of androgen receptor can cause androgen-insensitivity syndrome. Surgical removal of testosterone-producing gonads can result in loss of libido. Libido may be improved with testosterone treatment but not with estradiol in some forms of CAIS. A previously unreported AR mutation – p.Glu2_Met190del (c.2T>C) – is found in a CAIS patient and results in blunted AR transcriptional activity under testosterone treatment. Bioscientifica Ltd 2021-05-13 /pmc/articles/PMC8240814/ /pubmed/34152287 http://dx.doi.org/10.1530/EDM-21-0031 Text en © The authors https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Insight into Disease Pathogenesis or Mechanism of Therapy
Marino, Laura
Messina, Andrea
S Acierno, James
Phan-Hug, Franziska
J Niederländer, Nicolas
Santoni, Federico
La Rosa, Stefano
Pitteloud, Nelly
Testosterone-induced increase in libido in a patient with a loss-of-function mutation in the AR gene
title Testosterone-induced increase in libido in a patient with a loss-of-function mutation in the AR gene
title_full Testosterone-induced increase in libido in a patient with a loss-of-function mutation in the AR gene
title_fullStr Testosterone-induced increase in libido in a patient with a loss-of-function mutation in the AR gene
title_full_unstemmed Testosterone-induced increase in libido in a patient with a loss-of-function mutation in the AR gene
title_short Testosterone-induced increase in libido in a patient with a loss-of-function mutation in the AR gene
title_sort testosterone-induced increase in libido in a patient with a loss-of-function mutation in the ar gene
topic Insight into Disease Pathogenesis or Mechanism of Therapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240814/
https://www.ncbi.nlm.nih.gov/pubmed/34152287
http://dx.doi.org/10.1530/EDM-21-0031
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