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Petroli, Reginaldo J.
[1, 2, 3]
;
Hiort, Olaf
[1]
;
Struve, Dagmar
[1]
;
Gesing, Julia K.
[1]
;
Soardi, Fernanda C.
[2]
;
Spinola-Castro, Angela M.
[4]
;
Melo, Karla
[5]
;
Arnhold, Ivo J. Prado
[5]
;
Maciel-Guerra, Andrea T.
[6]
;
Guerra-Junior, Gil
[7]
;
Werner, Ralf
[1]
;
de Mello, Maricilda P.
[2]
Número total de Autores: 12
|
| Afiliação do(s) autor(es): | [1] Univ Lubeck, Dept Paediat & Adolescent Med, Div Paediat Endocrinol & Diabet, Lubeck - Germany
[2] Univ Estadual Campinas, Fac Ciencias Med, Ctr Biol Mol Engn Genet, Campinas - Brazil
[3] Univ Fed Alagoas, Hosp Univ Prof Alberto Antunes, Lab Genet Mol Humana, Setor Genet Med & Clin, Maceio - Brazil
[4] Univ Fed Sao Paulo, Dept Pediat, Sao Paulo - Brazil
[5] Univ Sao Paulo, Hosp Clin, Fac Med, Lab Hormonios & Genet Mol LIM 42, Div Endocrinol, Unidade Endocrinol Desenvolvimento, Sao Paulo - Brazil
[6] Univ Estadual Campinas, Fac Ciencias Med, Dept Genet Med, Campinas - Brazil
[7] Univ Estadual Campinas, Fac Ciencias Med, Dept Pediat, Campinas - Brazil
Número total de Afiliações: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | SEXUAL DEVELOPMENT; v. 11, n. 5-6, p. 238-247, 2017. |
| Citações Web of Science: | 3 |
| Resumo | |
Androgens are responsible for the development and maintenance of male sex characteristics. Dysfunctions in androgen action due to mutations in the androgen receptor gene (AR) can lead to androgen insensitivity syndrome (AIS) that can be classified as mild (MAIS), partial (PAIS), or complete (CAIS). We have analyzed functional effects of p.Ser760Thr, p.Leu831Phe, p.Ile899Phe, p.Leu769Val, and p.Pro905Arg mutations and the combination p.Gln799Glu + p.Cys807Phe that were identified in patients with PAIS or CAIS. The p.Leu769Val and p.Pro905Arg mutations showed complete disruption of AR action under physiological hormone concentrations; however, they differed in high DHT concentrations especially in the N/C terminal interaction assay. Mutations p.Ser760Thr, p.Leu831Phe, p.Ile899Phe presented transactivation activities higher than 20% of the wild type in physiological hormone concentrations and increased with higher DHT concentrations. However, each one showed a different profile in the N/C interaction assay. When p.Gln799Glu and p.Cys807Phe were analyzed in combination, transactivation activities <10% in physiologic hormone conditions indicated an association with a CAIS phenotype. We conclude that the functional analysis elucidated the role of mutant ARs, giving clues for the molecular mechanisms associated with different clinical AIS manifestations. Differences in hormone-dependent profiles may provide a basis for the response to treatment in each particular case. (C) 2017 S. Karger AG, Basel (AU) | |
| Processo FAPESP: | 08/01964-5 - Análise molecular do gene do receptor de andrógenos (AR) em pacientes 46,XY com ambiguidade genital e produção normal de testosterona |
| Beneficiário: | Reginaldo José Petroli |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |
| Processo FAPESP: | 09/08320-9 - Investigação de mutações nos genes ar e SRD5A2 em pacientes 46,XY recém-nascidos e pré-púberes com ambiguidade genital |
| Beneficiário: | Maricilda Palandi de Mello |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |