Active secretion of thyroxine into bile: the role of tissue thyroxine-binding sites.

1. An investigation has been made into factors regulating the secretion of thyroid hormones into bile. The preparation employed was the isolated rat liver perfused with a modified Tyrode solution.2. Tracer amounts of radioactive thyroxine were injected into the Tyrode solution just before its entry into the liver. This allowed the thyroxine-binding sites in the tissue to capture most of the injected hormone. It was found that this tissue-bound hormone was then gradually secreted into the bile and that the process could be resolved into two components. There was a steady, continuous secretion of hormone, which maintained a fairly constant bile:liver ratio in thyroxine concentration of about 2.3. There was also, superimposed upon this, an extra transient secretion of thyroxine occurring just after the injection. This transient effect was abolished by injecting the hormone at 22 degrees C and it was probably due to the sudden flood of free thyroxine into the tissue during the 15 sec injection period.3. Very similar results were obtained with tri-iodothyronine except that the secretion process maintained a higher bile:liver ratio of about 3.7.4. The secretion mechanism was extremely sensitive to changes in temperature and it was able to generate very high concentrations of free thyroxine in the bile. It was concluded that the over-all process was probably an active one.5. The presence of 30% bovine serum in the perfusion fluid did not reduce the bile:liver thyroxine ratio even though it caused a massive fall in the amount of thyroxine in the tissue.6. These results show that the rate of thyroxine secretion into bile is determined by the total amount of thyroxine trapped in the tissue. It is not directly related to the concentration of free thyroxine in the perfusing medium.7. It is suggested that the secretion mechanism works from a small intracellular pool of free thyroxine which is in rapid exchange with the large pool of tissue-bound hormone, and that thyroxine exchange between this small intracellular pool and the free thyroxine pool in the plasma is relatively slow.