Marja Rutgers

The role of sulfation in thyroid hormone metabolism

Sulfate conjugation is a significant metabolic reaction for thyroxine and especially so for triiodothyronine and lower iodothyronines in rats. Triiodothyronine sulfation has also been demonstrated in humans. Sulfation accelerates the deiodinative breakdown of iodothyronines by the type I iodothyronine deiodinase in liver and thus represents a rate-limiting step in one of the elimination pathways of thyroid hormone.

Accumulation of plasma triiodothyronine sulfate in rats treated with propylthiouracil.

Triiodothyronine sulfate (T3S) is rapidly deiodinated by the propylthiouracil (PTU)-sensitive type I deiodinase. Here we examined the effects of PTU on plasma T3S levels in rats after intravenous administration of radiolabeled T3 or T3S. Sephadex LH-20 chromatography and high-performance liquid chromatography were used to quantify conjugated and nonconjugated iodothyronines, and iodide was measured as the TCA-soluble radioactivity. In control rats, radioiodide was the main metabolite of both T3 and T3S. Plasma T3S was cleared more rapidly than plasma T3 despite increased binding to plasma proteins. PTU reduced plasma iodide levels by 66 and 78% after T3 and T3S, respectively, and decreased plasma clearance of T3S by 81%. However, PTU had no effect on plasma T3 clearance but increased plasma T3S from injected T3 4.2 times. Biliary excretion of injected T3S was less than 20% in normal rats, in contrast to 70% within 4 h in PTU-treated rats. In conclusion, T3S is an important intermediate in the in vivo metabolism of T3 in rats and accumulates in plasma if type I deiodination is inhibited.

On the enterohepatic cycle of triiodothyronine in rats; importance of the intestinal microflora

Until 70 h after a single iv injection of 10 uCi [125I]triiodothyronine (T3), normal rats excreted 15.8 +/- 2.8% of the radioactivity with the feces and 17.5 +/- 2.7% with the urine, while in intestine-decontaminated rats fecal and urinary excretion over this period amounted to 25.1 +/- 7.2% and 23.6 +/- 4.0% of administered radioactivity, respectively (mean +/- SD, n = 4). In fecal extracts of decontaminated rats 11.5 +/- 6.8% of the excreted radioactivity consisted of T3 glucuronide (T3G) and 10.9 +/- 2.8% of T3 sulfate (T3S), whereas no conjugates were detected in feces from normal rats. Until 26 h after ig administration of 10 uCi [125I]T3, integrated radioactivity in blood of decontaminated rats was 1.5 times higher than that in normal rats. However, after ig administration of 10 uCi [125I]T3G or [125I]T3S, radioactivity in blood of decontaminated rats was 4.9- and 2.8-fold lower, respectively, than in normal rats. The radioactivity in the serum of control animals was composed of T3 and iodide in proportions independent of the tracer injected, while T3 conjugates represented less than 10% of serum radioactivity. These results suggest an important role of the intestinal microflora in the enterohepatic circulation of T3 in rats.

Metabolism of Thyroid Hormone in Liver

The thyroid gland produces predominantly the prohormone thyroxine (T4) together with a small amount of the biologically active hormone 3,3′,5-triiodothyronine (T3). In normal humans and rats 80% of circulating T3 is derived from outer ring deiodination (ORD) of T4 in peripheral tissues. T3 is further degraded by inner ring deiodination (IRD) to 3,3′-T2. T4 and T3 are also metabolized by glucuronide (G) and sulfate (S) conjugation.