Linked Life Data

9092800

Source:http://linkedlifedata.com/resource/pubmed/id/9092800

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1997-8-26
pubmed:abstractText
TSHbeta is a subunit of TSH that is uniquely expressed and regulated in the thyrotrope cells of the anterior pituitary gland. Thyroid hormone receptors (TR) are known to mediate T3 suppression of TSHbeta gene expression at the level of promoter activity. The role of other nuclear receptors in regulation of this gene is less clearly defined. Retinoid X receptors (RXR) are a family of nuclear transcription factors that function both as 9-cis-retinoic acid (RA) ligand-dependent receptors and heterodimeric partners with TR and other nuclear receptors. Recently, the RXR isoform, RXRgamma, has been identified in the anterior pituitary gland and found to be restricted to thyrotrope cells within the pitutiary. In this report, we have further characterized the distribution of RXRgamma1, the thyrotrope-restricted isoform of RXRgamma, in murine tissues and different cell types. We have found that RXRgamma1 mRNA and protein are expressed in the TtT-97 thyrotropic tumor, but not the thyrotrope-variant alphaTSH cells or somatotrope-derived GH3 cells. Furthermore, we have studied the effects of RXRgamma1 on TSHbeta promoter activity and hormone regulation in these pituitary-derived cell types. Both T3 and 9-cis-RA independently suppressed promoter activity in the TtT-97 thyrotropes. Interestingly, the combination of ligands suppressed promoter activity more than either alone, indicating that these hormones may act cooperatively to regulate TSHbeta gene expression in thyrotropes. The RXRgamma1 isoform was necessary for the 9-cis-RA-mediated suppression of TSHbeta promoter activity in alphaTSH and GH3 cells, both of which lack this isoform. RXRbeta, a more widely distributed isoform, did not mediate these effects. Finally, we showed that the murine TSHbeta promoter region between -200 and -149 mediated a majority of the 9-cis-RA suppression of promoter activity in thyrotropes. This region is distinct from the T3-mediated response region near the transcription start site. These data suggest that retinoids can mediate TSHbeta gene regulation in thyrotropes and the thyrotrope-restricted isoform, RXRgamma1, is required for this effect.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
481-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9092800-Animals, pubmed-meshheading:9092800-Base Sequence, pubmed-meshheading:9092800-Blotting, Western, pubmed-meshheading:9092800-Chromosome Mapping, pubmed-meshheading:9092800-DNA-Binding Proteins, pubmed-meshheading:9092800-Mice, pubmed-meshheading:9092800-Molecular Sequence Data, pubmed-meshheading:9092800-Nuclear Proteins, pubmed-meshheading:9092800-Pituitary Gland, pubmed-meshheading:9092800-Promoter Regions, Genetic, pubmed-meshheading:9092800-RNA, Messenger, pubmed-meshheading:9092800-Receptors, Retinoic Acid, pubmed-meshheading:9092800-Retinoid X Receptors, pubmed-meshheading:9092800-Thyrotropin, pubmed-meshheading:9092800-Tissue Distribution, pubmed-meshheading:9092800-Transcription Factors, pubmed-meshheading:9092800-Transfection, pubmed-meshheading:9092800-Tretinoin, pubmed-meshheading:9092800-Tumor Cells, Cultured
pubmed:year
1997
pubmed:articleTitle
The thyrotrope-restricted isoform of the retinoid-X receptor-gamma1 mediates 9-cis-retinoic acid suppression of thyrotropin-beta promoter activity.
pubmed:affiliation
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't