3-3--diiodothyronine-4-sulfate and triiodothyronine-sulfate

Earlier studies have shown that sulfoconjugation is a major pathway of thyroid hormone metabolism in fetal mammals. To assess the placental transfer of sulfoconjugates in the pregnant sheep model, we measured 3,3',5-triiodothyronine (T(3)) sulfate (T(3)S), 3, 3'-diiodothyronine sulfate (T(2)S), and T(3) concentrations in fetal serum and in maternal serum and urine after T(3)S infusion to the fetus (n = 5) or the ewe (n = 6). Maternal infusion of T(3)S did not increase fetal serum T(2)S, T(3)S, or T(3) concentrations. In contrast, fetal infusion of T(3)S produced significant increases in maternal serum T(2)S and T(3)S but not T(3) concentrations. Fetal T(3)S infusion also increased maternal urine excretion of T(3)S. However, the 4-h cumulative maternal urinary excretion of T(2)S and T(3)S after fetal T(3)S infusion was less than the excretion observed after fetal infusion of equimolar amounts of T(3) in our previous study. It is concluded that fetal serum T(2)S and T(3)S can be transferred to maternal compartments. However, compared with T(3), these sulfoconjugates may be less readily transferred.

Topics: Animals; Diiodothyronines; Female; Fetus; Maternal-Fetal Exchange; Pregnancy; Sheep; Thyroid Gland; Triiodothyronine

Previous studies have shown that the inner ring deiodination (IRD) of T3 and the outer ring deiodination (ORD) of 3,3'-diiodothyronine are greatly enhanced by sulfate conjugation. This study was undertaken to evaluate the effect of sulfation on T4 and rT3 deiodination. Iodothyronine sulfate conjugates were chemically synthetized. Deiodination was studied by reaction of rat liver microsomes with unlabeled or outer ring 125I-labeled sulfate conjugate at 37 C and pH 7.2 in the presence of 5 mM dithiothreitol. Products were analyzed by HPLC or after hydrolysis by specific RIAs. T4 sulfate (T4S) was rapidly degraded by IRD to rT3S, with an apparent Km of 0.3 microM and a maximum velocity (Vmax) of 530 pmol/min X mg protein. The Vmax to Km ratio of T4S IRD was increased 200-fold compared with that of T4 IRD. However, formation of T3S by ORD of T4S could not be observed. The rT3S formed was rapidly converted by ORD to 3,3'-T2 sulfate, with an apparent Km of 0.06 microM and a Vmax of 516 pmol/min X mg protein. The enzymic mechanism of the IRD of T4S was the same as that of the deiodination of nonsulfated iodothyronines, as shown by the kinetics of stimulation by dithiothreitol or inhibition by propylthiouracil. The IRD of T4S and the ORD of rT3 were equally affected by a number of competitive inhibitors, suggesting a single enzyme for the deiodination of native and sulfated iodothyronines. In conjunction with previous findings on the deiodination of T3S, these results suggest that sulfation leads to a rapid and irreversible inactivation of thyroid hormone.

Topics: Animals; Diiodothyronines; Dithiothreitol; Iodide Peroxidase; Iodine Radioisotopes; Kinetics; Microsomes, Liver; Peroxidases; Propylthiouracil; Rats; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse