Linked Life Data

11396657

Source:http://linkedlifedata.com/resource/pubmed/id/11396657

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-6-8
pubmed:abstractText
Mutations that totally disrupt androgen receptor function cause the well known testicular feminizing syndrome or complete androgen insensitivity syndrome, wherein a 46 XY individual is completely feminized at birth. Recently it has been increasingly obvious that androgen receptor mutations not only result in the complete androgen insensitivity syndrome, but can cause a wide spectrum of milder insensitivity syndromes including ambiguous genitalia in newborn infants, and 'idiopathic' male infertility in otherwise normal males. Characterization of the molecular and structural mechanisms of androgen receptor dysfunction in these cases has led to directed hormonal therapy. Thus the differential response of a Met807Thr mutant androgen receptor to dihydrotestosterone but not testosterone, have been used to restore male genital development in an infant with partial AIS. Of greater significance, because they affect larger numbers of patients, are the mutations and polymorphisms that result in depressed spermatogenesis and male infertility in phenotypic males. Studies involving Singaporean, Australian, North American and Japanese subjects have established that increases in length of a trinucleotide repeat (CAG) tract, encoding a polyglutamine stretch in the transactivation domain of the androgen receptor, are associated with increased risk of defective spermatogenesis and undermasculinization. Independent of the CAG repeats, missense amino-acid substitutions in the ligand-binding domain, involving residues 727, 798 and 886 cause infertility through a novel mechanism. Pathogenicity is transmitted, not through defective ligand binding, but through defective protein-protein interactions between receptor domains and coactivator proteins that are essential for gene transcription. Elucidation of the molecular and structural basis of androgen receptor dysfunction in these cases allows precise genetic counseling and can lead to the design of rational hormonal therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1040-872X
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
315-21
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Sex, infertility and the molecular biology of the androgen receptor.
pubmed:affiliation
Department of Obstetrics & Gynaecology, National University of Singapore, Republic of Singapore.
pubmed:publicationType
Journal Article, Review