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

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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_5EFE487E7386
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
Testosterone-induced increase in libido in a patient with a loss-of-function mutation in the AR gene.
Journal
Endocrinology, diabetes & metabolism case reports
Author(s)
Marino L., Messina A., S Acierno J., Phan-Hug F., J Niederländer N., Santoni F., La Rosa S., Pitteloud N.
ISSN
2052-0573 (Print)
ISSN-L
2052-0573
Publication state
Published
Issued date
01/06/2021
Peer-reviewed
Oui
Volume
2021
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
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.
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.
Pubmed
Open Access
Yes
Create date
22/06/2021 16:53
Last modification date
17/07/2021 6:35
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