Thyroid hormone metabolism in a transthyretin-null mouse strain

Area of Science:

• Endocrinology
• Molecular Biology
• Physiology

Background:

• Transthyretin (TTR) is a key plasma protein for thyroid hormone transport in rodents.
• Thyroid hormone homeostasis is crucial for metabolic regulation and development.
• Understanding TTR's role is vital for comprehending thyroid hormone dynamics.

Purpose of the Study:

• To investigate the physiological consequences of TTR absence in mice.
• To determine the impact of TTR deficiency on thyroid hormone levels and tissue activity.
• To validate the free hormone hypothesis for thyroxine uptake.

Main Methods:

• Generation of TTR-deficient mice via targeted gene disruption.
• Measurement of total and free thyroxine (T4), triiodothyronine, and thyrotropin-stimulating hormone levels.
• Assay of liver deiodinase-I and UDP-glucuronosyltransferase activity, and brain deiodinase-II activity.

Main Results:

• TTR-deficient mice exhibited a 50% decrease in total plasma T4 but maintained normal free T4 levels.
• Increased T4 binding to thyroxine-binding globulin was observed in mutant serum.
• Thyroid hormone tissue activity and liver glucuronidation remained unaffected.

Conclusions:

• TTR-deficient mice are euthyroid despite the absence of the primary plasma T4 carrier.
• Normal free hormone levels in TTR-deficient mice support the free hormone hypothesis.
• TTR plays a significant role in T4 transport but is not essential for maintaining thyroid hormone homeostasis.