Maternal thyroxine and 3,5,3'-tri-iodothyronine kinetics in near-term pregnant rats at two different levels of hypothyroidism

Department of Human and Animal Physiology, Agricultural University, Wageningen, The Netherlands.

Thyroid hormones are extremely important for development of the fetal central nervous system. Thyroidectomy results in severe hypothyroidism. In this study two levels of maternal hypothyroidism were reached by administration of different amounts of thyroxine (T4) and 3,5,3'-tri-iodothyronine (T3) to thyroidectomized pregnant rats. We examined the production, distribution and transport of T4 and T3 by performing a kinetic experiment (three-compartment analysis) with intact and thyroidectomized near-term pregnant rats which received either very low (Tx + lowTH) or normal (Tx + TH) doses of T4 and T3. Despite administration of normal doses of thyroid hormones, plasma TSH was still elevated in the Tx + TH rats, meaning that these rats were still mildly hypothyroid. The Tx + lowTH rats were markedly hypothyroid, the plasma T4 and T3 levels being very low. In the mildly hypothyroid rats the transport of T4 from plasma to the fast pool and vice versa was decreased compared with intact near-term pregnant rats. This could imply that much less T4 is transported to the feto-placental compartment. Liver type I deiodinase was decreased, resulting in lowered plasma T3 values. In the markedly hypothyroid rats all pools and rates of transport of T4 and T3 were greatly decreased. In conclusion, even mild hypothyroidism, despite normal plasma T4 values, results in significant changes, especially in maternal T4 transport. We suggest that even mild maternal hypothyroidism will have a negative effect on the availability of maternal T4 for fetuses.