Linked Life Data

16172422

Source:http://linkedlifedata.com/resource/pubmed/id/16172422

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-9-30
pubmed:abstractText
Rodents studies suggest that androgens are involved in sex-specific differences in blood pressure. In humans, there is no difference in blood pressure between boys and girls, but after puberty, blood pressure increases more in men than in women. We investigated androgen-dependent regulation of the alpha-subunit of the epithelial sodium channel (alphaEnaC) in human kidney and in the human renal cell line immortalized human renal proximal tubular cell line (HKC-8). We used microarray technique to analyze androgen-dependent gene regulation and performed quantitative RT-PCR for verification. Promoter constructs for human alphaENaC were used in transfection studies to analyze the regulation by testosterone. We investigated the in vivo effect of testosterone on alphaENaC in a rat model and used the mouse collecting duct cell line M-1 for transepithelial electrophysiological measurements. The androgen receptor (AR) was expressed in male kidney and HKC-8 cells. AlphaENaC mRNA expression increased 2- to 3-fold after treatment with testosterone in HKC-8 cells. The induction by testosterone was completely blocked by adding the AR antagonist flutamide. Analysis of the alphaENaC promoter sequence identified a putative AR response element (ARE) located 140 nucleotides upstream from the transcription start site. HKC-8 cell transfection studies showed that testosterone directly upregulated gene expression via this ARE. In vivo, testosterone treatment of orchiectomized rats resulted in an increased renal alphaENaC mRNA expression. In testosterone-treated mouse M-1 cells, amiloride caused a significant stronger decrease in short circuit current than in control cells. These data show that alphaENaC expression is directly regulated by androgens in vitro and in vivo and highlight a potential mechanism explaining the reported gender differences in blood pressure.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
787-98
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16172422-Animals, pubmed-meshheading:16172422-Cells, Cultured, pubmed-meshheading:16172422-Electrophysiology, pubmed-meshheading:16172422-Epithelial Sodium Channel, pubmed-meshheading:16172422-Gene Expression, pubmed-meshheading:16172422-Genes, Reporter, pubmed-meshheading:16172422-Humans, pubmed-meshheading:16172422-Kidney, pubmed-meshheading:16172422-Kidney Tubules, Collecting, pubmed-meshheading:16172422-Kidney Tubules, Proximal, pubmed-meshheading:16172422-Male, pubmed-meshheading:16172422-Mice, pubmed-meshheading:16172422-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:16172422-Orchiectomy, pubmed-meshheading:16172422-Polymerase Chain Reaction, pubmed-meshheading:16172422-Promoter Regions, Genetic, pubmed-meshheading:16172422-Receptors, Androgen, pubmed-meshheading:16172422-Sodium Channels, pubmed-meshheading:16172422-Steroids, pubmed-meshheading:16172422-Testosterone
pubmed:year
2005
pubmed:articleTitle
Androgen receptor-mediated regulation of the alpha-subunit of the epithelial sodium channel in human kidney.
pubmed:affiliation
Division of Medical Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't