| Full text | |
| Author(s): Show less - |
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]
Total Authors: 12
|
| Affiliation: | [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
Total Affiliations: 7
|
| Document type: | Journal article |
| Source: | SEXUAL DEVELOPMENT; v. 11, n. 5-6, p. 238-247, 2017. |
| Web of Science Citations: | 3 |
| Abstract | |
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) | |
| FAPESP's process: | 08/01964-5 - Molecular analysis of the androgen receptor gene (AR) in patients 46,XY presenting genital ambiguity and normal testosterone production |
| Grantee: | Reginaldo José Petroli |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 09/08320-9 - Serching for mutations on ar and SRD5A2 genes in 46,XY newborn and pre-pubarche patients with genital ambiguity |
| Grantee: | Maricilda Palandi de Mello |
| Support Opportunities: | Regular Research Grants |