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Related Concept Videos

Synthesis and Regulation of Thyroid Hormones01:20

Synthesis and Regulation of Thyroid Hormones

Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...

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Comparative study on 2,2',4,5,5'-pentachlorobiphenyl-mediated decrease in serum thyroxine level between C57BL/6 and

Yoshihisa Kato1, Sekihiro Tamaki, Koichi Haraguchi

  • 1Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa 769-2193, Japan. kato@kph.bunri-u.ac.jp

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Area of Science:

  • Environmental Toxicology
  • Endocrinology
  • Pharmacokinetics

Background:

  • Thyroxine (T4) is a crucial thyroid hormone regulated by transthyretin (TTR) in serum.
  • Polychlorinated biphenyls (PCBs) are environmental contaminants with known endocrine-disrupting effects.
  • The impact of PCBs on T4 homeostasis, particularly involving TTR, requires further elucidation.

Purpose of the Study:

  • To investigate the effects of 2,2',4,5,5'-pentachlorobiphenyl (PentaCB) on serum thyroxine (T4) levels.
  • To examine the role of transthyretin (TTR) in mediating PentaCB-induced alterations in T4 pharmacokinetics.
  • To determine the tissue distribution of T4 following PentaCB exposure.

Main Methods:

  • Utilized wild-type (WT) and TTR-deficient (TTR-null) mice for comparative analysis.
  • Administered a single intraperitoneal injection of PentaCB to mice.
  • Quantified serum T4, serum T4-TTR complex, and tissue accumulation of radiolabeled T4 ([(125)I]T4).

Main Results:

  • PentaCB significantly decreased serum total T4 and T4-TTR complex in WT mice.
  • PentaCB also slightly reduced serum T4 in TTR-null mice.
  • [(125)I]T4 clearance from serum was accelerated by PentaCB, with enhanced liver accumulation and increased liver-to-serum T4 concentration ratios in both mouse strains.

Conclusions:

  • PentaCB exposure leads to decreased serum T4 levels primarily through increased hepatic T4 accumulation.
  • In WT mice, PentaCB-induced hepatic T4 accumulation is largely attributed to the inhibition of T4-TTR complex formation.
  • These findings highlight the disruption of thyroid hormone homeostasis by PCBs and the critical role of TTR in this process.