Endocrine Abstracts

Purpose: Disruption in thyroid hormone homeostasis by environmental chemicals during the prenatal and/or neonatal period might lead to developmental disorders since thyroid hormones (T3/T4) play a critical role in growth and the differentiation of many tissues including the central nervous system. Neonatally given T3 or T4 disrupts the thyroid hormone system resulting in decreased serum T4 level in the adulthood in rats. In the present study, changes in gene expression profile in the pituitary-thyroid-liver axis by neonatal hyperthyroidism were examined to identify possible neonatal effects of thyroid hormone disrupting chemicals.

Materials and Methods: Male F344 rats were exposed to T3, T4 or amiodarone (0.04, 4 and 0.4 mg/kg bw, respectively) at PND 1, 3 and 5. Animals were sacrificed at 8 weeks old and total RNAs were extracted from the pituitary, thyroid and liver. Expression of the genes related to the thyroid hormone homeostasis was measured by the quantitative RT-PCR method. Serum T3 and T4 were determined by ELISA.

Results and Conclusions: 1) Neonatal hyperthyroidism resulted in lower serum T4 level in rats at 8 weeks old. 2) Expressions in thyroid hormone receptor alpha, T3 responsive genes (RLT3-2 and RLT3-24) and an enzyme related to T3/T4 metabolism, Sult1C3, increased in the thyroid and liver tissues in T3/T4 treated groups. 3) Amiodarone showed the similar effects on the gene expression profile with T3 albeit in a lesser extent. The present study demonstrated that neonatal exposure to thyroid hormones irreversibly altered the expression profile of the genes related to the thyroid hormone homeostasis. In addition, amiodarone, a chemical exhibiting thyroid hormone-like activity, showed the similar neonatal effects. The changes in gene expression profile in the pituitary-thyroid-liver axis could be markers for the neonatal effects by thyroid hormone disrupting chemicals.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.