Is the kidney a major storage site for thyroxine as thyroxine glucuronide?

Background: Previous studies have shown that thyroxine (T4) is stored as T4 glucuronide (T4G) in the kidney, and that 24 hours after administration of [(125)I]T4 to mice, 17% of the radioactivity was present in the kidneys, whereas only 4% was found in the liver. The present study was carried out to determine the relative amounts of conjugated and unconjugated T4 and 3,5,3'-triiodothyronine (T3) in the kidney and liver, and whether the conjugated hormones are extracted from tissues using our established extraction protocols, and detected in our radioimmunoassays (RIAs) for T4 and T3.

Methods: Mice were injected with 10 μCi [(125)I]T4 or [(125)I]T3 and 24 hours later, the labeled compounds present in serum, kidney, liver, and urine were extracted and analyzed by paper chromatography before and after treatment with β-glucuronidase. In addition, the amounts of endogenous T4 and T3 in extracts of mouse kidney and liver were measured by RIA before and after treatment with β-glucuronidase.

Results: After [(125)I]T4, more than 95% of the total kidney and liver radioactivity was extracted, and in the kidney, almost all of it was present in a conjugated form, mostly as T4G. The liver also contained T4G, but none was present in serum or urine. T3 glucuronide (T3G) was also found in the kidney and liver after the administration of [(125)I]T3. Analysis by RIA of the endogenous T4 content in extracts of kidney before and after hydrolysis by β-glucuronidase revealed that a substantial fraction of the T4 in both tissues was present as T4G, and the T4G was not detected in the RIA. Furthermore, the combined T4+T4G content in the kidney expressed per gram of tissue was significantly higher than that in the liver or serum. In contrast, the kidney content of T3+T3G was very low compared with that of T4+T4G.

Conclusions: In summary, we have shown that the kidney stores a significant amount of T4 as T4G. Since T4G deconjugation can occur rapidly in the kidney, it is possible that this tissue participates in maintaining extrathyroidal serum T4 homeostasis.