Iodide uptake by the thyroid is an active process. Iodine deficiency and pregnancy are known to influence thyroid hormone metabolism. The aim of this study was to clarify the effects of iodine deficiency and pregnancy on iodide uptake by the thyroid. Radioiodide was injected intravenously into nonpregnant and 19-day pregnant rats receiving a normal or marginally iodine-deficient diet. The uptake of radioiodide by the thyroid was measured continuously for 4 h. The absolute iodide uptake by the maternal and fetal thyroid glands at 24 h was calculated by means of the urinary specific activity. Pregnancy resulted in a decrease in the absolute thyroidal iodide uptake. Marginal iodine deficiency had no effect on the absolute iodide uptake by the maternal thyroid. The decreased plasma inorganic iodide was compensated by an increase in thyroidal clearance. A similar compensation was not found for the fetus; the uptake of iodide by the fetal thyroid decreased by 50% during marginal iodine deficiency. This can lead to diminished thyroid hormone production, which will have a negative effect on fetal development, especially of the brain.

In the pregnant rat near term thyroxine (T4) and 3,5,3'-triiodothyronine (T3) concentrations are lower in plasma and extrathyroidal tissues, except T3 in the brain. To study the changes in T4 and T3 kinetics a bolus injection of [125I]T4 and [131I]T3 was administered to nonpregnant controls and rats 14 and 19 days pregnant. Physiological parameters of the production, interpool transport, distribution, and metabolism of T4 and T3 were estimated by means of a three-compartment model. The production and partition of T4 remained unchanged during pregnancy. The total distribution volume of T4 was enlarged. On day 19 the plasma clearance rate was doubled, and transport to the fast pool was more than tripled. The rate of production of T3 was slightly diminished. The plasma clearance rate was increased, but no changes were found in the interpool transport rates. These results suggest that in the pregnant rat near term the increased transport of T4 is responsible for the distribution of the available T4 between the maternal and the fetal compartment.

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 (T 4 ) and 3,5,3 0 -tri-iodothyronine (T 3 ) to thyroidectomized pregnant rats. We examined the production, distribution and transport of T 4 and T 3 by performing a kinetic experiment (three-compartment analysis) with intact and thyroidectomized near-term pregnant rats which received either very low (Tx þ lowTH) or normal (Tx þ TH) doses of T 4 and T 3 . Despite administration of normal doses of thyroid hormones, plasma TSH was still elevated in the Tx þ TH rats, meaning that these rats were still mildly hypothyroid. The Tx þ lowTH rats were markedly hypothyroid, the plasma T 4 and T 3 levels being very low. In the mildly hypothyroid rats the transport of T 4 from plasma to the fast pool and vice versa was decreased compared with intact near-term pregnant rats. This could imply that much less T 4 is transported to the feto-placental compartment. Liver type I deiodinase was decreased, resulting in lowered plasma T 3 values. In the markedly hypothyroid rats all pools and rates of transport of T 4 and T 3 were greatly decreased. In conclusion, even mild hypothyroidism, despite normal plasma T 4 values, results in significant changes, especially in maternal T 4 transport. We suggest that even mild maternal hypothyroidism will have a negative effect on the availability of maternal T 4 for fetuses.

During pregnancy maternal thyroid hormones are of great importance for normal development of the central nervous system of the fetus. Iodine deficiency of the mother can result in an impaired development of the fetal brain. In large areas of the world iodine intake is moderately low. To study the effects of marginal iodine deficiency (MID) on the production, distribution, and transport of thyroxine (T 4 ) and 3,5,3 0 -tri-iodothyronine (T 3 ) in nonpregnant and near-term pregnant rats we performed kinetic experiments (three-compartment analysis). Despite unchanged plasma T 4 and T 3 during MID, the production and plasma clearance rates of T 4 decreased 30% (P = 0.01) in MID nonpregnant (MID-C) rats. For T 3, the plasma clearance rate was increased 70% (P = 0.046), while the T 3 production was more than doubled (P = 0.042) in MID-C rats. In MID near-term pregnant rats T 3 production was decreased 20% (P = 0.04). Hepatic deiodinase type I activity increased during MID in both nonpregnant and pregnant rats. It appears that during MID, rats are able to maintain their euthyroid status. The pronounced increase in transport of T 4 from plasma to the fast pool observed in pregnant rats on a normal iodine diet did not occur during MID. In conclusion, in rats MID affects maternal thyroid hormone metabolism, thus influencing the availability of maternal T 4 for the fetus. European Journal of Endocrinology 138 713-718

3,5,30 -Tri-iodothyronine (T 3 ) is produced by the thyroid and locally, by monodeiodination of thyroxine (T 4 ), in the peripheral tissues. During pregnancy the thyroid hormone status in rats is altered: plasma and tissue levels of T 4 and T 3 are decreased. We investigated the effects of pregnancy on the contribution of T 3 produced locally in the maternal tissues by administering a continuous infusion of [125 I]T 4 and [ 131 I]T 3 . The transport of T 4 to almost all maternal organs diminished. Less T 3 was transported from the plasma to brown adipose tissue (BAT), liver, kidney and pituitary, in contrast to the ovary where an increase was found. In BAT and brain the amount of locally produced T 3 decreased, despite the known increase in deiodinase type II activity in the brain while in liver the contribution of locally produced T 3 remained constant, despite a known increase in deiodinase type I activity during pregnancy. This discrepancy between deiodinase activities and locally produced T 3 can be explained by an insufficient availability of T 4 . Thus, we conclude that in the rat a decrease in maternal T 4 concentration, together with the transport of T 4 to the feto-placental compartment, results indirectly in a diminished availability of T 3 in the maternal organs.