Preserved Fertility in a Patient with Gynecomastia Associated with the p.Pro695Ser Mutation in the Androgen Receptor

Preserved Fertility in a Patient with Gynecomastia Associated with the p.Pro695Ser Mutation in the Androgen Receptor

Author Petroli, Reginaldo J. Google Scholar
Hiort, Olaf Google Scholar
Struve, Dagmar Google Scholar
Maciel-Guerra, Andrea T. Google Scholar
Guerra-Junior, Gil Google Scholar
Mello, Maricilda Palandi de Google Scholar
Werner, Ralf Google Scholar
Institution Universidade Estadual de Campinas (UNICAMP)
Universidade Federal de São Paulo (UNIFESP)
Med Univ Lubeck
Abstract The androgen insensitivity syndrome (AIS) is described as a dysfunction of the androgen receptor (AR) in 46, XY individuals, which can be associated with mutations in the AR gene or can be due to unknown mechanisms. Different mutations in AIS generally cause variable phenotypes that range from a complete hormone resistance to a mild form usually associated with male infertility. the purpose of this study was to search for mutations in the AR gene in a fertile man with gynecomastia and to evaluate the influence of the mutation on the AR transactivation ability. Sequencing of the AR gene revealed the p.Pro695Ser mutation. It is located within the AR ligand-binding domain. Bioinformatics analysis indicated a deleterious role, which was verified after testing transactivation activity and N-/C-terminal (N/C) interaction by in vitro expression of a reporter gene and 2-hybrid assays. p.Pro695Ser showed low levels of both transactivation activity and N/C interaction at low dihydrotestosterone (DHT) conditions. As the ligand concentration increased, both transactivation activity and N/C interaction also increased and reached normal levels. Therefore, this study provides functional insights for the p.Pro695Ser mutation described here for the first time in a patient with mild AIS. the expression profile of p.Pro695Ser not only correlates to the patient's phenotype, but also suggests that a high-dose DHT therapy may overcome the functional deficit of the mutant AR. (C) 2014 S. Karger AG, Basel
Keywords Androgen insensitivity syndrome
Androgen receptor gene
AR p.Pro695Ser mutation
Gynecomastia
Male fertility
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
University of Lubeck
European Union under the 7th Framework Programme (EuroDSD)
Grant number FAPESP: 2009/08320-9
FAPESP: 2008/01964-5
European Union under the 7th Framework Programme (EuroDSD): 201444
Date 2014-01-01
Published in Sexual Development. Basel: Karger, v. 8, n. 6, p. 350-355, 2014.
ISSN 1661-5425 (Sherpa/Romeo, impact factor)
Publisher Karger
Extent 350-355
Origin http://dx.doi.org/10.1159/000368862
Access rights Closed access
Type Article
Web of Science ID WOS:000348061000002
URI http://repositorio.unifesp.br/handle/11600/37292

Show full item record




File

File Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Search


Browse

Statistics

My Account