Thyroid hormones and lipid metabolism

Thyroid hormone (T3) and its receptor (TR) have the diverse effects on the lipid metabolism and hypothyroidism causes hypercholesterolaemia characterized by increased levels of low-density ripoproteins (LDL). There are multiple TR isoforms such as TRalpha1, TRbeta1 and TRbeta2, of which expressions...

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Bibliographic Details
Published inNihon rinshō Vol. 64; no. 12; p. 2323
Main Authors Sasaki, Shigekazu, Kawai, Kotaro, Honjo, Yumiko, Nakamura, Hirotoshi
Format Journal Article
LanguageJapanese
Published Japan 01.12.2006
Subjects
Animals
Cholesterol, LDL - blood
Drug Design
Humans
Hypercholesterolemia - drug therapy
Hypercholesterolemia - etiology
Hypothyroidism - complications
Lipid Metabolism - genetics
Phenyl Ethers
Phenylacetates
Protein Isoforms - physiology
Receptors, Cytoplasmic and Nuclear - physiology
Receptors, Thyroid Hormone - physiology
Transcription Factors
Transcription, Genetic
Triiodothyronine - agonists
Triiodothyronine - analogs & derivatives
Triiodothyronine - physiology
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Summary:Thyroid hormone (T3) and its receptor (TR) have the diverse effects on the lipid metabolism and hypothyroidism causes hypercholesterolaemia characterized by increased levels of low-density ripoproteins (LDL). There are multiple TR isoforms such as TRalpha1, TRbeta1 and TRbeta2, of which expressions are known to be tissue-specific. For example, TRbeta1 is the major TR in the liver while T3 action is mediated via TRalpha1 in the heart. The X-ray crystallography of the ligand-binding domain of TRs enabled the development of TRbeta isoform specific T3 analogues including GC1. Without tachycardia, GC1 selectively targets the TRbeta1 in the liver and decreases cholesterol levels with more potent efficacy than that of atorvastatin, a potent HMG-CoA reductase. However, the reduction of serum TSH by GC1 should be overcome in future. Current reports also describe the existence of the complex cross-talks in the lipid metabolism between TR and other nuclear hormone receptors including peroxisome proliferator -activated receptors (PPARs), liver X receptor alpha (LXRalpha) and farnesoid X receptors (FXRs). Understanding for the function of TRs and other nuclear factors may provide the new approach to the control of hypercholesterolaemia.
ISSN:0047-1852