Regulation of iodothyronine deiodinases in the Pax8-/- mouse model of congenital hypothyroidism

Thyroid hormones are essential for a variety of developmental and metabolic processes. Congenital hypothyroidism (CHT) results in severe defects in the development of different tissues, in particular brain. As an animal model for CHT, we studied Pax8-/- mice, which are born without a thyroid gland. We determined the expression of iodothyronine deiodinase D1 in liver and kidney, D2 in brain and pituitary, and D3 in brain, as well as serum T4, T3, and rT3 levels in Pax8-/- vs. control mice during the first 3 wk of life. In control mice, serum T4 and T3 were undetectable on the day of birth (d 0) and increased to maximum levels on d 15. In Pax8-/- mice, serum T4 and T3 remained below detection limits. Serum rT3 was high on d 0 in both groups and rapidly decreased in Pax8-/-, but not in control mice. Hepatic and renal D1 activities and mRNA levels were low on d 0 and increased in control mice roughly parallel to serum T4 and T3 levels. In Pax8-/- mice, tissue D1 activities and mRNA levels remained low. Cerebral D2 activities were low on d 0 and increased to maximum levels on d 15, which were approximately 10-fold higher in Pax8-/- than in control mice. D2 mRNA levels were higher in Pax8-/- than in control mice only on d 21. Cerebral D3 activities and mRNA levels were high on d 0 and showed a moderate decrease between d 3 and 15, with values slightly lower in Pax8-/- than in control mice. One day after the injection of 200 ng T4 or 20 ng T3/g body weight, tissue deiodinase activities and mRNA levels were at least partially restored toward control levels, with the exception of cerebral D3 activity. In conclusion, these findings show dramatic age and thyroid state-dependent changes in the expression of deiodinases in central and peripheral tissues of mice during the first 3 wk of life.

• View at Publisher
• View at Pubmed
• View at Scopus
• View at Web of Science