An androgen receptor mutation in the direct vicinity of the proposed C-terminal alpha-helix of the ligand binding domain containing the AF-2 transcriptional activating function core is associated with complete androgen insensitivity.
Mol Cell Endocrinol
; 148(1-2): 47-53, 1999 Feb 25.
Article
em En
| MEDLINE
| ID: mdl-10221770
ABSTRACT
Subjects with androgen insensitivity syndromes (AIS) are characterized by a 46, XY karyotype, presence of testes, normal or elevated androgen levels in blood, and impairment of the usual response to androgens associated with various aberrations of male differentiation and virilization ranging from slightly undervirilized men to phenotypic females. Here we describe a novel proline to serine mutation in codon 892 (exon 8) of the androgen receptor in a patient with complete androgen insensitivity. The mutation is located in the direct vicinity of the proposed C-terminal alpha-helix of the ligand binding domain containing the AF-2 transcriptional activating function core. Investigation of androgen binding in cultured testicular fibroblasts of the patient revealed a reduced AR binding capacity (11 fmol/mg protein) and a highly elevated Kd value (3.1 nM) in comparison to control genital skin fibroblasts. Cotransfection studies with an androgen-responsive reporter gene revealed a diminished transactivation property of the mutant androgen receptor.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Resistência a Andrógenos
/
Receptores Androgênicos
/
Estrutura Secundária de Proteína
/
Mutação Puntual
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article