5α-reduction of epitestosterone is catalysed by human SRD5A1 and SRD5A2 and increases androgen receptor transactivation.
J Steroid Biochem Mol Biol
; 241: 106516, 2024 07.
Article
em En
| MEDLINE
| ID: mdl-38582131
ABSTRACT
Epitestosterone is a stereoisomer of the active androgen testosterone and its circulating concentrations are similar to those of testosterone in women and children. However, its biological function and pathways of metabolism remain unknown. The structural similarity to testosterone suggests a potential function in the modulation of androgen receptor signalling. It is well established that the conversion of testosterone to 5α-dihydrotestosterone enhances local androgen receptor signalling. In this study, we show that epitestosterone is metabolized to 5α-dihydroepitestosterone by both human steroid 5α-reductase isoforms, SRD5A1 and SRD5A2. Using two different variations of a reporter assay for transactivation of the human androgen receptor, we show that epitestosterone is a partial AR agonist and that the 5α-reduction of epitestosterone increases its androgenic activity. In line with this, we show that 5α-reduction of epitestosterone reduces its ability to antagonize 5α-dihydrotestosterone-induced androgen receptor transactivation. In conclusion, we provide evidence that steroid 5α-reductases regulate the modulatory effect of epitestosterone on androgen receptor signalling.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
3-Oxo-5-alfa-Esteroide 4-Desidrogenase
/
Receptores Androgênicos
/
Ativação Transcricional
/
Epitestosterona
/
Proteínas de Membrana
Limite:
Humans
Idioma:
En
Revista:
J Steroid Biochem Mol Biol
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
Reino Unido