Linked Life Data

12068007

Source:http://linkedlifedata.com/resource/pubmed/id/12068007

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2002-9-23
pubmed:abstractText
The influence of estrogen on the development of the male reproductive system may be interrupted in a subset of partial androgen insensitivity syndrome (PAIS) patients. PAIS describes a wide range of male undermasculinization resulting from mutations in the androgen receptor (AR) or steroid metabolism enzymes that perturb androgen-AR regulation of male sex organ development. In this study, we are interested in determining if PAIS-derived AR mutants that respond normally to androgen have altered responses to estrogen in the presence of ARA70, a coregulator previously shown to enhance 17beta-estradiol E2-induced AR transactivation. The wild-type AR (wtAR) and two PAIS AR mutants, AR(S703G) and AR(E709K), all bind to androgen and E2 and subsequently translocate to the nucleus. Whereas ARA70 functionally interacts with the wtAR and the PAIS AR mutants in response to androgen, E2 only promotes the functional interaction between ARA70 and the wtAR but not the PAIS AR mutants. ARA70 increases E2 competitive binding to the wtAR in the presence of low level androgen and also retards E2 dissociation from the wtAR. ARA70 is present in both the cytoplasm and the nucleus of various mouse testicular cells during early embryogenesis day 16, at postpartum day 0 during estradiol synthesis and in the Leydig cells at postpartum day 49. ARA70 may be unable to modulate the PAIS AR mutants-E2 binding, diminishing the effect of E2 via AR during male reproductive system development in patients with such mutations. Therefore, the presence of ARA70 in the testosterone and E2-producing Leydig cells may enhance the overall activity of AR during critical stages of male sex organ development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
36499-508
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12068007-Animals, pubmed-meshheading:12068007-COS Cells, pubmed-meshheading:12068007-Cell Nucleus, pubmed-meshheading:12068007-Estradiol, pubmed-meshheading:12068007-Female, pubmed-meshheading:12068007-Humans, pubmed-meshheading:12068007-Immunohistochemistry, pubmed-meshheading:12068007-Leydig Cells, pubmed-meshheading:12068007-Ligands, pubmed-meshheading:12068007-Male, pubmed-meshheading:12068007-Microscopy, Fluorescence, pubmed-meshheading:12068007-Mutation, pubmed-meshheading:12068007-Nuclear Receptor Coactivators, pubmed-meshheading:12068007-Oncogene Proteins, pubmed-meshheading:12068007-Plasmids, pubmed-meshheading:12068007-Precipitin Tests, pubmed-meshheading:12068007-Protein Binding, pubmed-meshheading:12068007-Receptors, Androgen, pubmed-meshheading:12068007-Time Factors, pubmed-meshheading:12068007-Trans-Activators, pubmed-meshheading:12068007-Transcription Factors, pubmed-meshheading:12068007-Transcriptional Activation, pubmed-meshheading:12068007-Transfection, pubmed-meshheading:12068007-Tumor Cells, Cultured, pubmed-meshheading:12068007-Two-Hybrid System Techniques
pubmed:year
2002
pubmed:articleTitle
Mutations in the helix 3 region of the androgen receptor abrogate ARA70 promotion of 17beta-estradiol-induced androgen receptor transactivation.
pubmed:affiliation
George Whipple Laboratory for Cancer Research, Department of Pathology, University of Rochester, Rochester, New York 14642, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't