Linked Life Data

21292823

Source:http://linkedlifedata.com/resource/pubmed/id/21292823

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-3-30
pubmed:abstractText
Mice deficient in thyroid hormone receptor ? (TR?) display hypersensitivity to thyroid hormone (TH), with normal serum TSH but diminished serum T(4). Our aim was to determine whether altered TH metabolism played a role in this hypersensitivity. TR? knockout (KO) mice have lower levels of rT(3), and lower rT(3)/T(4) ratios compared with wild-type (WT) mice. These alterations could be due to increased type 1 deiodinase (D1) or decreased type 3 deiodinase (D3). No differences in D1 mRNA expression and enzymatic activity were found between WT and TR?KO mice. We observed that T(3) treatment increased D3 mRNA in mouse embryonic fibroblasts obtained from WT or TR?KO mice, but not in those from TR?KO mice. T(3) stimulated the promoter activity of 1.5 kb 5'-flanking region of the human (h) DIO3 promoter in GH3 cells after cotransfection with hTR? but not with hTR?. Moreover, treatment of GH3 cells with T(3) increased D3 mRNA after overexpression of TR?. The region necessary for the T(3)-TR? stimulation of the hD3 promoter (region -1200 to -1369) was identified by transfection studies in Neuro2A cells that stably overexpress either TR? or TR?. These results indicate that TR? mediates the up-regulation of D3 by TH in vitro. TR?KO mice display impairment in the regulation of D3 by TH in both brain and pituitary and have reduced clearance rate of TH as a consequence of D3 deregulation. We conclude that the absence of TR? results in decreased clearance of TH by D3 and contributes to the TH hypersensitivity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1944-9917
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
575-83
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Thyroid hormone receptor ? and regulation of type 3 deiodinase.
pubmed:affiliation
Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural