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Thyroid hormone dependent regulation of target genes and their physiological significance

Ya-Hui Huang1, Ming-Ming Tsai, Kwang-Huei Lin

  • 1Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, No. 259, Wunhua 1st Rd., Gueishan Township, Taoyuan County 333, Taiwan (R.O.C.).

Chang Gung Medical Journal
|October 22, 2008
PubMed

Insights

Thyroid hormone (T3) regulates gene expression via nuclear receptors. This study identified 149 T3-regulated genes in liver cells, impacting blood coagulation, inflammation, and metabolism.

Area of Science:

  • Molecular Endocrinology
  • Gene Regulation
  • Hepatoma Cell Biology

Background:

  • Thyroid hormone (T3) is crucial for growth and development, mediated by nuclear thyroid hormone receptors (TRs).
  • Understanding T3's regulatory mechanisms in liver cells is vital for comprehending its physiological roles.

Purpose of the Study:

  • To investigate the mechanism of target gene regulation by T3 in a TR alpha-overexpressing hepatoma cell line (HepG2-TR alpha).
  • To identify genes regulated by T3 and elucidate their physiological significance.

Main Methods:

  • cDNA microarrays were employed to screen for T3-regulated genes.
  • Quantitative-reverse transcription polymerase chain reaction (Q-RT-PCR) and promoter assays were used for validation.
  • Cycloheximide was utilized to distinguish direct from indirect transcriptional regulation.

Main Results:

  • Approximately 149 genes were positively regulated by T3, including fibrinogen, transferrin, fibronectin (FN), androgen receptor (AR)-associated protein (ARA70), and SULT2A1.
  • T3-mediated regulation was confirmed to occur primarily at the transcriptional level.
  • Similar gene regulation patterns were observed in both human and rat models, suggesting conserved mechanisms.

Conclusions:

  • T3 plays a significant role in regulating genes involved in blood coagulation, inflammation, metabolism, and cell proliferation.
  • The findings may explain the link between thyroid diseases and dysregulated inflammatory and clotting profiles.
  • This research provides insights into the broader physiological impact of thyroid hormone action.

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