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Related Experiment Videos

Plasma protein regulation by thyroid hormone.

K-H Lin1, H-Y Lee, C-H Shih

  • 1Department of Biochemistry, Chang-Gung University, Taoyuan, Taiwan, Republic of China. khlin@mail.cgu.edu.tw

The Journal of Endocrinology
|December 6, 2003
PubMed
Summary
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Thyroid hormones (THs) directly regulate the expression of numerous plasma proteins, including transferrin, by activating thyroid hormone receptors (TRs). This study reveals THs up-regulate some proteins and down-regulate others, impacting liver-based protein synthesis.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Hepatology

Background:

  • Thyroid hormones (THs) are crucial regulators of physiological processes.
  • Thyroid hormone receptors (TRs) mediate TH action, primarily through transcriptional regulation.
  • The impact of TRs on plasma protein gene expression remains largely unexplored.

Purpose of the Study:

  • To investigate the role of thyroid hormone receptors (TRs) in regulating plasma protein gene expression.
  • To identify specific plasma proteins whose expression is modulated by THs via TRs.

Main Methods:

  • Utilized human hepatocellular carcinoma cell lines (HepG2).
  • Performed cDNA microarray analysis to screen for TH-regulated genes.
  • Conducted immunoblot, Northern blot, and nuclear run-on assays for detailed analysis of transferrin regulation.

Related Experiment Videos

  • Investigated the directness of TH action using cyclohexamide treatment.
  • Main Results:

    • THs significantly altered the expression of multiple plasma proteins.
    • Up-regulated proteins include transferrin, prothrombin, angiotensinogen, haptoglobin, alpha-2-HS-glycoprotein, complement, lipoproteins, and fibrinogen.
    • Down-regulated proteins include clusterin, alpha-2-macroglobulin precursor, prothymosin alpha, and alpha-fetoprotein.
    • Transferrin induction by THs was confirmed to be time- and dose-dependent, occurring at the transcriptional level and directly mediated by TRalpha1.

    Conclusions:

    • Thyroid hormones directly regulate the expression of a wide array of plasma proteins synthesized in the liver.
    • Transferrin gene expression is directly induced by THs, likely through interaction with a specific promoter element.
    • These findings elucidate a novel mechanism of TH action on hepatic gene expression impacting crucial plasma proteins.