Mutations of androgen receptor gene in androgen insensitivity syndromes

Sultan, Charles; Lumbroso, Serge; Poujol, Nicolas; Belon, Charles; Boudon, C; Lobaccaro, Jean‐Marc

doi:10.1016/0960-0760(93)90178-y

Cited by 93 publications

(44 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The two most essential androgens are testosterone and five alpha-dihydrotestosterone [4]. The actions are mediated by androgen receptor [8]. Both the subjects of this case report presented with increased testosterone level which reinforces the androgen resistance resulting characteristics of these cases.…”

Section: Case Descriptionsupporting

confidence: 52%

Androgen Insensitivity Syndrome Among Cousin Sisters- A Rare Entity

Ramamurthy¹,

Karuppusamy²

2018

IJAR

View full text Add to dashboard Cite

Androgen insensitivity syndrome (AIS), is a X-linked disorder characterized by resistance to androgen caused by mutation of androgen receptor gene in which XY karyotype individuals exhibit female phenotype.AIS is characterised by evidence of feminization (under masculinization) of the external genitalia at birth, abnormal secondary sexual development at puberty, and infertility in individuals with 46 XY karyotype.We are presenting here a familial case of complete androgen insensitivity syndrome in south Indian Population. 46 XY karyotype was found in two subjects who were cousin sisters with female phenotype,who presented with primary amenorrhoea. Comet assay was done, which showed results comparable with normal males. In both girls' inguinal gonads was present which was removed and hormonal therapy with estrogen was given to prevent osteoporosis. Androgen insensitivity syndrome can be inherited as an X linked disorder as evidenced by previous studies.

show abstract

Section: Case Descriptionsupporting

confidence: 52%

Androgen Insensitivity Syndrome Among Cousin Sisters- A Rare Entity

Ramamurthy¹,

Karuppusamy²

2018

IJAR

View full text Add to dashboard Cite

show abstract

“…Recently, various mutations have been observed in the androgen receptor gene in cases of complete and incomplete testicular feminization. [1][2][3] We analyzed the sequence of genomic DNA of the androgen receptor gene in a case of complete testicular feminization and a novel point mutation substituting codon 892 proline for leucine in the androgen-binding domain was observed. Single missense mutations at the same position have been reported, namely 12 cases in codon 855 (exon 7), 10 in codon 774 (exon 6) and eight in codon 866 (exon 7), 3 It is necessary to demonstrate the absence of sensitivity to androgen or defects of the androgen receptor in target tissues in order to clarify the role of androgen receptor gene mutations in this disease.…”

Section: Discussionmentioning

confidence: 99%

“…Such mutations are considered to be due to androgen insensitivity in tissues and the absence of differentiation to normal male. [1][2][3] Laparoscopic surgery is being used extensively as treatment for urological diseases and laparoscopic orchiectomy has been found very useful for minimal invasive therapy, especially for testicular feminization patients.…”

Section: Introductionmentioning

confidence: 99%

A case of complete testicular feminization: Laparoscopic orchiectomy and analysis of androgen receptor gene mutation

et al. 1999

View full text Add to dashboard Cite

Background: Analysis of an androgen receptor gene mutation and a bilateral laparoscopic orchiectomy were performed on a 19-year-old patient diagnosed as a case of complete testicular feminizaton. Methods: DNA sequencing of an androgen receptor gene mutation and laparoscopic orchiectomy were performed. Results: A novel point mutation substituting a proline residue (CCG) for a leucine residue (CTG) was observed in codon 892 of exon 8 in the hormone-binding domain of the androgen receptor gene. Bilateral intra-abdominal testes were resected uneventfully by means of laparoscopic orchiectomy. Conclusion:We conclude that genetic analysis of androgen receptor gene mutation is essential for diagnosis of teon and laparoscopic orchiectomy is a useful therapeutic alteration as a minimally invasive treatment.

show abstract

“…Specifically in reference to the AR-LBD, it had been inferred from DNA sequence homology (Wurtz et al 1996) and mutation studies (Doesburg et al 1997;Gottlieb et al 1998;Taplin et al 1999;Wurtz et al 1996) that the carbonyl oxygen of the A-ring and the C17β hydroxylic oxygen of the D-ring in DHT most likely interact through H-bonds with Arg 752 in helix 5 and Thr 877 in helix 11 in AR-LBD, respectively, because mutation of these residues caused a complete androgeninsensitivity syndrome (Sultan et al 1993) and altered ligand specificity (Veldscholte et al 1990). Recent crystallographic determination of the AR-LBD bound to a steroidal-type ligand (R1881), and a more recent homology modeling study that considered a variety of nonsteroidal AR ligands bound to the LBD, provide evidence to support and refine this view (Marhefka et al 2001;Matias et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Interaction of organophosphate pesticides and related compounds with the androgen receptor.

Tamura

Yoshikawa

Gaido

et al. 2003

Environ Health Perspect

View full text Add to dashboard Cite

Identification of several environmental chemicals capable of binding to the androgen receptor (AR) and interfering with its normal function has heightened concern about adverse effects across a broad spectrum of environmental chemicals. We previously demonstrated AR antagonist activity of the organophosphate (OP) pesticide fenitrothion. In this study, we characterized AR activity of analogues of fenitrothion to probe the structural requirements for AR activity among related chemicals. AR activity was measured using HepG2 human hepatoma cells transfected with human AR plus an androgen-responsive luciferase reporter gene, MMTV-luc. AR antagonist activity decreased as alkyl chain length of the phosphoester increased, whereas electron-donating properties of phenyl substituents of the tested compounds did not influence AR activity. Oxon derivatives of fenitrothion, which are more likely to undergo hydrolytic degradation, had no detectable AR antagonist activity. Molecular modeling results suggest that hydrogen-bond energies and the maximum achievable interatomic distance between two terminal H-bond capable sites may influence both the potential to interact with the AR and the nature of the interaction (agonist vs. antagonist) within this series of chemicals. This hypothesis is supported by the results of recent AR homology modeling and crystallographic studies relative to agonist- and antagonist-bound AR complexes. The present results are placed in the context of structure-activity knowledge derived from previous modeling studies as well as studies aimed toward designing nonsteroidal antiandrogen pharmaceuticals. Present results extend understanding of the structural requirements for AR activity to a new class of nonsteroidal, environmental, OP-related chemicals.

show abstract

Mutations of androgen receptor gene in androgen insensitivity syndromes

Cited by 93 publications

References 63 publications

Androgen Insensitivity Syndrome Among Cousin Sisters- A Rare Entity

Androgen Insensitivity Syndrome Among Cousin Sisters- A Rare Entity

A case of complete testicular feminization: Laparoscopic orchiectomy and analysis of androgen receptor gene mutation

Interaction of organophosphate pesticides and related compounds with the androgen receptor.

Contact Info

Product

Resources

About