Linked Life Data

15126566

Source:http://linkedlifedata.com/resource/pubmed/id/15126566

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-5-5
pubmed:abstractText
We investigated the mechanisms regulating estrogen receptor (ER) expression in human aortic smooth muscle cells (HASMCs) and the mechanisms by which estradiol inhibits HASMC growth. The autologous down-regulation pathway involves binding of liganded ER to the ER gene, thus suppressing transcription. Blockade of this pathway with sense and AS-OLIGOs to ERs up-regulated the expression of ERalpha but not ERbeta. Activation of the autologous down-regulation pathway with ER agonists down-regulated the expression of ERalpha but not ERbeta. The proteasomal degradation pathway entails ubiquination of liganded ER, followed by proteasome-mediated degradation. Blockade of the proteasomal degradation pathway increased the expression of ERbeta. Up-regulation of ERalpha by AS-OLIGOs did not increase the antimitogenic effects of estradiol on HASMCs; the estradiol metabolites 2-hydroxyestradiol and 2-methoxyestradiol were more potent inhibitors of HASMC growth, compared with estradiol; and blockade of metabolism of estradiol to hydroxyestradiols and methoxyestradiols abrogated the inhibitory effects of estradiol on HASMC growth. We conclude that, in HASMCs: 1) the expression of ERalpha is regulated by the autologous downregulation pathway; 2) the expression of ERbeta is governed by the proteasomal degradation pathway; and 3) the antigrowth effects of estradiol are not mediated by ERalpha, but rather by metabolism of estradiol to methoxyestradiols.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2373-81
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Differential regulation of estrogen receptor subtypes alpha and beta in human aortic smooth muscle cells by oligonucleotides and estradiol.
pubmed:affiliation
Department of Obstetrics and Gynecology, Clinic for Endocrinology, University Hospital Zurich, 8091 Zurich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't