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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2003-4-28
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pubmed:abstractText |
Steroid receptor coactivator-1 (SRC-1) is a transcription cofactor that enhances the hormone-dependent action mediated by the thyroid hormone (TH) receptor (TR) as well as other nuclear receptors. However, it is not known whether the SRC-1-mediated activation of TH-regulated gene transcription is TR isoform specific in the pituitary. We generated mice that were deficient in TRalpha and SRC-1 (TRalpha(0/0)SRC-1(-/-)), as well in TRbeta and SRC-1 (TRbeta(-/-)SRC-1(-/-)), and thyroid function tests and effects of TH deprivation and TH treatment were compared with wild-type mice or mice with deletion of either TRs or SRC-1 alone. We have shown that 1) TRbeta(-/-)SRC-1(-/-) mice demonstrate more severe TH resistance than either the SRC-1(-/-) or TRbeta(-/-) mice; the additive effect indicates that SRC-1 has an independent role in TH action over that of TRbeta; 2) SRC-1 facilitates TRbeta and TRalpha-mediated down-regulation of TSH, as TRalpha(0/0)SRC-1(-/-) mice demonstrate TH resistance rather than hypersensitivity as seen in TRalpha(0/0)mice; and 3) a compensatory increase in SRC-1 expression is associated with the TH hypersensitivity seen in TRalpha-deficient animals. We conclude that SRC-1 action in the pituitary mediates TH action via specific TR subtypes.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Histone Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Ncoa1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ncoa3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Coactivator 1,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Coactivator 2,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Coactivator 3,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Thyroid Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Thyroid Hormone Receptors alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Thyroid Hormone Receptors beta,
http://linkedlifedata.com/resource/pubmed/chemical/Thyroid Hormones,
http://linkedlifedata.com/resource/pubmed/chemical/Thyrotropin,
http://linkedlifedata.com/resource/pubmed/chemical/Thyrotropin, beta Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Triiodothyronine
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0888-8809
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
882-94
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12576486-Animals,
pubmed-meshheading:12576486-Cell Nucleus,
pubmed-meshheading:12576486-Female,
pubmed-meshheading:12576486-Histone Acetyltransferases,
pubmed-meshheading:12576486-Male,
pubmed-meshheading:12576486-Mice,
pubmed-meshheading:12576486-Mice, Mutant Strains,
pubmed-meshheading:12576486-Nuclear Receptor Coactivator 1,
pubmed-meshheading:12576486-Nuclear Receptor Coactivator 2,
pubmed-meshheading:12576486-Nuclear Receptor Coactivator 3,
pubmed-meshheading:12576486-Pituitary Gland,
pubmed-meshheading:12576486-RNA, Messenger,
pubmed-meshheading:12576486-Receptors, Thyroid Hormone,
pubmed-meshheading:12576486-Thyroid Function Tests,
pubmed-meshheading:12576486-Thyroid Hormone Receptors alpha,
pubmed-meshheading:12576486-Thyroid Hormone Receptors beta,
pubmed-meshheading:12576486-Thyroid Hormone Resistance Syndrome,
pubmed-meshheading:12576486-Thyroid Hormones,
pubmed-meshheading:12576486-Thyrotropin,
pubmed-meshheading:12576486-Thyrotropin, beta Subunit,
pubmed-meshheading:12576486-Trans-Activators,
pubmed-meshheading:12576486-Transcription Factors,
pubmed-meshheading:12576486-Triiodothyronine
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pubmed:year |
2003
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pubmed:articleTitle |
Thyroid hormone receptor-specific interactions with steroid receptor coactivator-1 in the pituitary.
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pubmed:affiliation |
Department of Medicine, University of Chicago, Illinois, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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