A possible mechanism for 2,2',4,4',5,5'-hexachlorobiphenyl-mediated decrease in serum thyroxine level in mice

Area of Science:

• Environmental Toxicology
• Endocrinology

Background:

• Polychlorinated biphenyls (PCBs) are environmental contaminants with known endocrine-disrupting effects.
• Thyroxine (T₄) is a critical thyroid hormone regulating metabolism.
• Understanding PCB-induced alterations in thyroid hormone homeostasis is crucial for risk assessment.

Purpose of the Study:

• To investigate the impact of 2,2',4,4',5,5'-hexachlorobiphenyl (CB153) on serum total thyroxine (T₄) levels in mice.
• To elucidate the mechanisms underlying CB153-induced changes in T₄ homeostasis, including hepatic metabolism and serum protein binding.

Main Methods:

• Administration of CB153 (100mg/kg, ip) to C57BL/6 (TCDD-sensitive) and DBA/2 (TCDD-resistant) mice.
• Measurement of serum total T₄, hepatic T₄-UDP-glucuronosyltransferase (T₄-UGT), and serum thyroid-stimulating hormone (TSH) levels.
• Assessment of [(125)I]T₄ binding to serum proteins and analysis of biliary excretion of [(125)I]T₄ and its glucuronide.

Main Results:

• CB153 treatment markedly decreased serum total T₄ levels in both mouse strains without affecting hepatic T₄-UGT or serum TSH.
• No significant changes in [(125)I]T₄ binding to serum transport proteins were observed.
• CB153 exposure led to increased hepatic accumulation of [(125)I]T₄ in both strains, with higher percentages observed in C57BL/6 mice.

Conclusions:

• CB153 exposure induces a significant reduction in serum total T₄ levels in mice.
• The primary mechanism for this T₄ reduction is enhanced hepatic accumulation of T₄, rather than altered T₄ metabolism or serum binding.
• These findings highlight the liver as a key target organ for CB153's effects on thyroid hormone homeostasis.