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Thyroid hormone. Basis for its hypocholesterolemic effect.

G C Ness1

  • 1Department of Biochemistry and Molecular Biology, University of South Florida, College of Medicine, Tampa.

The Journal of the Florida Medical Association
|June 1, 1991
PubMed
Summary
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Thyroid hormone significantly impacts cholesterol levels by altering gene expression in the liver. It decreases LDL cholesterol and increases HDL cholesterol, ultimately lowering overall serum cholesterol.

Area of Science:

  • Endocrinology
  • Metabolism
  • Molecular Biology

Background:

  • The liver plays a central role in maintaining cholesterol homeostasis.
  • Thyroid hormone influences cholesterol metabolism by interacting with nuclear receptors in liver cells.
  • Thyroid hormone affects the expression of genes critical for cholesterol regulation.

Purpose of the Study:

  • To investigate the molecular mechanisms by which thyroid hormone modulates cholesterol homeostasis in the liver.
  • To elucidate the specific effects of thyroid hormone on the expression of key genes involved in lipid metabolism.

Main Methods:

  • Analysis of gene expression changes in liver tissue following thyroid hormone administration.
  • Identification of potential thyroid hormone responsive elements in the promoter region of the cholesterol 7 alpha hydroxylase gene.

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Main Results:

  • Thyroid hormone decreases the expression of apolipoprotein B-100 (apo B-100), a major component of low-density lipoprotein (LDL).
  • Thyroid hormone increases the expression of apolipoprotein A-I (apo A-I), a major component of high-density lipoprotein (HDL).
  • Thyroid hormone upregulates hepatic LDL receptor and cholesterol 7 alpha hydroxylase gene expression, with the latter showing a rapid response to low hormone doses.

Conclusions:

  • Thyroid hormone promotes a shift towards lower serum cholesterol levels through multiple coordinated actions.
  • These actions include reduced LDL synthesis, enhanced reverse cholesterol transport via HDL, increased LDL clearance from the blood, and accelerated cholesterol elimination as bile acids.
  • Thyroid hormone appears to exert a primary regulatory effect on cholesterol 7 alpha hydroxylase gene expression, potentially via identified responsive elements.