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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2002-7-11
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pubmed:abstractText |
High-affinity agonists for the retinoic acid X receptors (RXR) have pleotropic effects when administered to humans. These include induction of hypertriglyceridemia and hypothyroidism. We determined the effect of a novel high-affinity RXR agonist with potent antihyperglycemic effects on thyroid function of female Zucker diabetic rats and nondiabetic littermates and in db/db mice. In both nondiabetic and ZFF rats, AGN194204 causes a 70-80% decrease in thyrotropin (TSH), 3,3',5-triiodothyronine, and thyroxine (T(4)) concentrations. In the db/db mouse, AGN194204 causes a time-dependent decrease in thyroid hormone levels with the fall in TSH that was significant after 1 day of treatment preceding the fall in T(4) levels that was significant at 3 days of treatment. Treatment with AGN194204 caused an initial increase in hepatic 5'-deiodinase mRNA levels which then fell to undetectable levels by 3 days of treatment and continued to be low at 7 days of treatment. After treatment for 5 days with AGN194204, both wild-type and thyroid hormone receptor beta (TR beta(-/-))-deficient mice demonstrated a nearly 50% decrease in serum TSH and T(4) concentrations. The results suggest that a high-affinity RXR agonist with antihyperglycemic activity can cause central hypothyroidism independently of TR beta, the main mediator of hormone-induced TSH suppression.
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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/AGN 194204,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Unsaturated,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Thyroid Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoid X Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrahydronaphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Thyrotropin,
http://linkedlifedata.com/resource/pubmed/chemical/Thyroxine,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0193-1849
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
283
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
E326-31
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12110538-Animals,
pubmed-meshheading:12110538-Diabetes Mellitus,
pubmed-meshheading:12110538-Down-Regulation,
pubmed-meshheading:12110538-Fatty Acids, Unsaturated,
pubmed-meshheading:12110538-Female,
pubmed-meshheading:12110538-Hypothyroidism,
pubmed-meshheading:12110538-Ligands,
pubmed-meshheading:12110538-Male,
pubmed-meshheading:12110538-Mice,
pubmed-meshheading:12110538-Mice, Knockout,
pubmed-meshheading:12110538-Protein Isoforms,
pubmed-meshheading:12110538-Rats,
pubmed-meshheading:12110538-Rats, Wistar,
pubmed-meshheading:12110538-Rats, Zucker,
pubmed-meshheading:12110538-Receptors, Retinoic Acid,
pubmed-meshheading:12110538-Receptors, Thyroid Hormone,
pubmed-meshheading:12110538-Retinoid X Receptors,
pubmed-meshheading:12110538-Tetrahydronaphthalenes,
pubmed-meshheading:12110538-Thyroid Gland,
pubmed-meshheading:12110538-Thyrotropin,
pubmed-meshheading:12110538-Thyroxine,
pubmed-meshheading:12110538-Transcription Factors
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pubmed:year |
2002
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pubmed:articleTitle |
RXR receptor agonist suppression of thyroid function: central effects in the absence of thyroid hormone receptor.
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pubmed:affiliation |
Department of Medicine, Committee on Genetics and the J. P. Kennedy Jr. Mental Retardation Research Center, The University of Chicago, Chicago, Illinois 60637-1470, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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