Possible Importance of Thyroidal Iodine Compartments in the Adaptation of Thyroid Hormone Secretion to Antithyroid Drugs12

Abstract
Rats with either normal thyroid glands, hyperplastic goiters or colloid goiters were given 125I in the drinking water for 28 days. A single injection of 131I was then given and 4 hr later further hormone biosynthesis was blocked with propylthiouracil. During the following seven days the various isotopes of protein-bound iodine (PBI) in serum were measured. In rats with normal glands, the 131I-PBI derived from the young label declined rapidly while the 127I-PBI stayed nearly constant. The 125I-PBI (old label) declined at an intermediate rate. In hyperplastic goiters the 131I-PBI and the 125I-PBI declined at the same rate and only slightly faster than the 127I-PBI. In colloid goiters the 127I-PBI and the 125I-PBI declined very little and at an identical slow rate, while the 131I-PBI concentration dropped nearly at the same fast rate as in normal glands and in hyperplastic goiters. The data suggest that the two labels are distributed in different compartments of intrathyroidal hormone. The young label (131I) is confined to a compartment that turns over much faster than the pool of the old label (125I) or the total 127I. In hyperplastic goiters no slow compartment can be found and both isotopes turn over at the same fast rate. This shows that the response of the total serum hormone concentration to an inhibition of thyroidal hormone neosynthesis depends on the presence of sufficient hormone stores in slow thyroid compartments. It is suggested that the subdivision of intrathyroidal hormone stores into different compartments has important physiological implications in the control of thyroid hormone secretion. If hormone biosynthesis is diminished either by lack of dietary iodine or by antithyroid drugs, the hormone release of the slow compartment is initially little affected, but the secretion from the fast compartment falls off rapidly. The latter phenomenon will lead to a slight rapid fall in the peripheral circulating thyroid hormone level presumably sufficient to trigger additional TSH secretion. This in turn would increase the rate of hormone release from sluggish compartments and thereby maintain total serum PBI at nearly normal levels. The multicompartmental model thus may provide a much faster control of thyroid function by the TSH feedback system than a simple unicompartmental model. (Endocrinology91: 1154, 1972)