Identification of Thyroxine-Sulfate (T₄S) in Human Serum and Amniotic Fluid by a Novel T₄S Radioimmunoassay

Abstract

Recently, we identified significant amounts of thyroxine sulfate (T4S) in fetal sheep serum, meconium, bile, and amniotic and allantoic fluids. Little is known, however, about sulfate conjugation of thyroxine in humans. In this study, we employed a novel, sensitive T4S RIA to address this question. The rabbit antiserum was quite specific; T4, T3, rT3, and 3,3'-T2 showed less than 0.002% cross-reactivity. Other analogs cross-reacted less than 0.0001%. Only rT3S and T3S cross-reacted significantly (9.9% and 2.0%, respectively). The mean serum T4S concentration (ng/dL) was 8.6 in euthyroid subjects, 14.4 in hyperthyroid subjects, 5.0 in hypothyroid subjects, 5.9 in pregnancy, and 4.5 in patients with nonthyroid illnesses. T4S concentration in amniotic fluid from women at 18-19 weeks of gestation (25.5 ng/dL) was higher than that at 14-15 weeks of gestation (14.3 ng/dL). A significant rise in serum T4S was detected in hyperthyroid patients 1 day after ingestion of 1 g of ipodate. These data suggest that T4S is a normal component of human serum and amniotic fluid, and it is mostly derived from T4 peripherally and accumulates when type I 5'-monodeiodinating activity is low in fetuses or inhibited by drugs, such as ipodate.

Comparative thyroidology: thyroid gland location and iodothyronine dynamics in Mozambique tilapia (Oreochromis mossambicus Peters) and common carp (Cyprinus carpio L.)

“…injection with [ (Santini et al, 1993;Wu et al, 1992;Wu et al, 1993), and indirect evidence exists for thyroid hormone conjugates in the plasma of European plaice (Pleuronectes platessa L.) (Osborn and Simpson, 1969), the Mozambique tilapia appears to be the only vertebrate in which plasma thyroid hormone glucuronides are observed. By injection of trace amounts of radioiodide instead of radiolabelled thyroid hormones, we circumvented the possibility of altering the thyroid status of the fish.…”

Molecular aspects of thyroid hormone transporters, including MCT8, MCT10, and OATPs, and the effects of genetic variation in these transporters

“…Like OATP1B1, OATP1B3 preferentially transports the sulfated iodothyronines as well as rT 3 (unpublished data, WM van der Deure, ECH Friesema, RP Peeters & TJ Vissers). Under normal conditions, D1 in liver rapidly degradates rT 3 and sulfated iodothyronines, keeping the serum concentrations of these metabolites low (Chopra et al 1992, Wu et al 1992, Bianco et al 2002. However, serum iodothyronine sulfates and rT 3 levels are high in preterm infants and during critical illness, possibly due to decreased degradation (Chopra et al 1992, Peeters et al 2005.…”

Characterization of Human Iodothyronine Sulfotransferases1

“…Sulfation of T 4 is almost undetectable, not only with recombinant SULT1A1 and SULT1A3 but also in human liver and kidney. Nevertheless, high serum T 4 S levels have been detected in human newborns (14,15), suggesting sulfation of T 4 by other isoenzymes.…”

“…T 4 to rT 3 and T 3 to 3,3Ј-T 2 , is capable of catalyzing the deiodination of sulfated iodothyronines (10,11). 1 Serum concentrations of T 4 S, T 3 S, rT 3 S, and 3,3Ј-T 2 S are low in normal human subjects, but they are high in fetal and cord blood, in patients with nonthyroidal illness, and in patients treated with propylthiouracil or iopanoic acid, inhibitors of D1 (12)(13)(14)(15)(16)(17)(18)(19). The serum T 3 S/T 3 ratio is also increased in hypothyroid patients (13).…”