THE METABOLISM OF I131-LABELLED THYROID HORMONES IN THE HYPOPHYSIS AND BRAIN OF THE RABBIT1

Abstract

The distribution and metabolism of thyroid hormones in the brains and the hypophyses of normal rabbits was determined after intravenous administration of I131-labelled triiodothyronine or thyroxine. Triiodothyronine concentrated in the gray matter of the brain, principally in the region of the paraventricular nucleus and the median eminence, and, more heavily, in the hypophyseal lobes. The pattern of distribution of thyroxine was similar, but concentration was much less intense. Very little activity was detected in the adenohypophysis, although the existence of an extravascular thyroxine space there was determined. Triiodothyronine rapidly left the plasma, but uptake in the tissues was slower, reaching a peak after about two hours. This pattern of concentration in time may have been dependent on the formation of a previously postulated plasma-triiodothyronine complex as a precursor of the tissue triiodothyronine. It resulted in high concentration gradients between tissues and plasma. Levels as high as 751 for the neuro-hypophysis and 17:1 for the adenohypophysis were reached; the highest for the cerebrum and diencephalon were 1.6:1 and 1.5:1, respectively. Although thyroxine reached peak concentration in the tissues about as rapidly as triiodothyronine, its level remained more constant, a slower rate of metabolic degradation being indicated. With equal doses, about three times as much triiodothyronine as thyroxine was taken up by the tissues. This ratio may partly explain the differences in biological activity of the two substances. The uptake of each hormone was roughly proportional to the dose injected (0.5 and 4.0 [mu]g/kg for thyroxine; 0.5, 4.0 and 12.0 [mu]g/kg for triiodothyronine). Chromatographic analysis showed the presence of triiodothyronine in the brains and the hypophyses of animals receiving triiodothyronine. The presence of iodide in the hypophyses of such animals suggested deiodination of triiodothyronine in hypophyseal tissue. No other known metabolites of triiodothyronine were detected. In thyroxine-treated animals, thyroxine was present in the brain and both triiodothyronine and thyroxine were detected in the hypophysis.