A biologically based dose-response model for dietary iodide and the hypothalamic-pituitary-thyroid axis in the adult rat: evaluation of iodide deficiency.
Various indices of thyroid function were measured in rats at early (2 to 26 days) and at late (up to 55 weeks) intervals after the onset of an iodine deficient diet (LID). Control groups received the same diet with iodine-supplemented drinking water. The measurements included: thyroid total 127I concentration, thyroid weight, [131i] mit/[131i]dit and [131i]t3/[131i]t4 after a labeling period of 18--24 h, serum T4, serum T3, and serum TSH. In the acute experiments serum T4 was significantly decreased at 6--7 days. Thereafter, the decrease was rapid and progressive, and by 26 days serum T4 was reduced to undetectable levels (less than .05 mug per 100 ml). Thyroid T4 decreased more rapidly than serum T4, suggesting that the turnover rate of thyroid T4 increased soon after the onset of LID. Serum T3, in contrast to serum T4 showed no significant change during the 26 day period. Thyroid T3 decreased less rapidly than thyroid T4, but was greatly reduced by 26 days. Presumably the turnover rate of thyroih was slightly but significantly elevated at 4 days, before there was any detectable decrease in serum T4. Thereafter, the results were somewhat variable, but there appeared to be no significant further rise in serum TSH up to about day 15, despite the observation that serum T4 fell rapidly during this period. Only after 15 days did serum TSH display a sharp increase. It is apparent from these results that there is no simple inverse relationship between plasma T4 and plasma TSH. In the chronic experiments serum T4 remained undetectable. Serum T3 was decreased to about 50% of the normal level at 7 weeks but there appeared to be no further decrease even at 55 weeks. Serum TSH rose to very high levels at 12 weeks but showed no further increase thereafter. Thyroid 127I concentration reached its lowest value at 15 weeks and showed no further decrease. Thyroid weight, on the other hand, appeared to increase progressively. To evaluate the effect of severe iodine deficiency on thyroid status, rats that had been on LID for 3-4 months were exposed to a cold environment (4--5 C). Body temperature and survival rates were compared with those of matched controls receiving LID + KI drinking water. The body temperatures of the latter group increased significantly on exposure to cold, and all animals survived. On the other hand, the body temperature of rats on LID alone began to decrease about 5 days after the onset of cold exposure, and when the diet was sufficiently low in iodine the majority of the rats died within 15 days. These results suggest that thyroid function in severely iodine deficient rats is not adequate to meet the challenge of acute cold stress. In this sense, therefore, these animals may be daid to display signs of hypothyroidism.