Linked Life Data

12711391

Source:http://linkedlifedata.com/resource/pubmed/id/12711391

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2003-4-24
pubmed:abstractText
Gonadotropin-releasing hormone (GnRH) is a neuropeptide that plays a pivotal role in reproductive processes. In recent years, it has become clear that it is also an anti-proliferative agent. GnRH analogs are now used clinically in the treatment of prostate cancer as well as endometriosis and precocious puberty. The target cells of GnRH include the gonadotropes of the anterior pituitary gland and the cells of various hormone-dependent tumors. Only a few target genes have been identified in these cells, however, and little is known concerning their regulation by GnRH. Therefore, we used a quantitative microarray assay to identify the genes that are regulated by GnRH in a murine gonadotrope tumor cell line (LbetaT2). Treatment of LbetaT2 cells with GnRH agonist des-gly(10),[D-Ala(6)]GnRH (GnRHA) for 1 h resulted in alterations in the levels of expression of genes that ranged in magnitude from 1.3- to 159-fold, with a total of 232 genes exhibiting a twofold or greater alteration in expression compared to vehicle treated cells. Of these 232 genes, 149 were up-regulated and, surprisingly, 83 were down-regulated by GnRHA treatment. After 24 h of treatment, the expression of most of the genes that had exhibited altered expression after 1 h of treatment had returned to baseline levels. Moreover, a different profile was observed after 24 h of treatment with 208 genes exhibiting a twofold or greater alteration. Of these, 95 were up-regulated and 113 down-regulated. Most of the affected genes were not known to be responsive to GnRH prior to this study. Treatment with GnRHA was found to affect the expression of a diverse range of genes, including oncogenes and those that encode transcription factors, ion channel proteins, and cytoskeletal proteins as well as other proteins that are involved in signal transduction, the cell cycle, cell proliferation and apoptosis. The altered expression of six of the genes that were found by microarray analysis to be regulated by GnRHA was confirmed by semiquantitative reverse transcriptase-polymerase chain reaction. This is first application of the microarray technique in the study of the global profile of genes regulated by GnRH, and should prove to be a powerful tool for future analysis of the mechanisms by which GnRH regulates the expression of gonadotropins and the growth of tumor cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0378-1119
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
308
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
67-77
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Identification of distinct gene expression profiles associated with treatment of LbetaT2 cells with gonadotropin-releasing hormone agonist using microarray analysis.
pubmed:affiliation
Department of Medicine, University of Louisville, 570 South Preston Street, Baxter Building, Room 204 C, Louisville, KY 40202, USA. sskaka01@louisville.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.