Molecular mechanisms of human thyrocyte dysfunction induced by low concentrations of polychlorinated biphenyl 118...

Area of Science:

• Endocrinology
• Environmental Toxicology
• Molecular Biology

Background:

• Polychlorinated biphenyls (PCBs) are persistent organic pollutants with known adverse effects on human health.
• Previous research indicated PCB118 damages thyroid structure and reduces thyroid hormone levels.
• The precise molecular mechanisms underlying PCB-induced thyrocyte dysfunction require further elucidation.

Purpose of the Study:

• To investigate the molecular mechanisms of thyrocyte dysfunction induced by 2,3',4,4',5-pentachlorobiphenyl (PCB118) in human thyroid epithelial cells (HTECs).
• To explore the role of the Akt/FoxO3a/NIS signaling pathway in PCB118-induced thyroid cell dysfunction.

Main Methods:

• Monolayer cultured human thyroid epithelial cells (HTECs) were treated with varying concentrations of PCB118.
• Cell viability, apoptosis, and levels of thyroglobulin (Tg), thyroxine (T4), Akt, FoxO3a, and sodium/iodide symporter (NIS) were assessed.
• Western blotting and RT-PCR were used to analyze protein and mRNA expression, respectively.
• The effect of the PI3K inhibitor LY294002 was evaluated.

Main Results:

• PCB118 exposure, at concentrations not affecting cell viability, significantly decreased Tg and T4 levels.
• PCB118 increased Akt and phosphorylated Akt (p-Akt) levels, and induced a cytoplasmic shift of FoxO3a.
• Exposure to PCB118 significantly decreased NIS mRNA and protein expression, an effect blocked by LY294002.
• Increased p-FoxO3a was observed, suggesting Akt activation influences FoxO3a phosphorylation.

Conclusions:

• PCB118 induces thyrocyte dysfunction by modulating the Akt/FoxO3a/NIS signaling pathway.
• The findings suggest a mechanism where PCB118 disrupts thyroid hormone synthesis and transport.
• This research offers insights into potential interventions against PCB-induced thyroid damage.