Regulation of Thyroidal Deiodinase Activity*

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Abstract
In previous work with human multinodular goiters widely differing deiodinase activities were observed in different tissue samples of the same thyroid. Since all areas of a single gland must be exposed to an identical plasma TSH [thyrotropin] level, the findings suggested that TSH is not the only factor regulating deiodinase activity is a goitrous gland. The present investigation was designed to define the relative role of TSH and non-TSH-dependent factors in regulating deiodinase activity of the rat thyroid. After 7 days of goitrogen treatment, the deiodinase activity per g thyroid and per mg DNA was greatly increased with perchlorate (CIO4-) and 6-propyl-2-thiouracil plus CIO4-, and only slightly increased with propylthiouracil alone and with a low I diet. Despite the continuous rise of serum TSH with further treatment, deiodinase activity per mg DNA declined to well below peak levels after 1 more week and remained at this only slightly higher than normal value for many weeks irrespective of the goitrogenic regimen. Because of a progressive increase in thyroid gland size, total thyroidal deiodinase activity continued to rise for periods as long as 280 days. Deiodinase activity per g tissue or per mg DNA of rats receiving T4 [thyroxine] was significantly decreased after 7 days with no significant further decrease until day 50. Although deiodinase activity is indeed TSH dependent, other factors are also involved in regulating the enzyme activity. CIO4- enhances enzyme activity more than any other goitrogen for comparable TSH levels, whereas propylthiouracil is far more potent in promoting goiter growth. Deiodinase activity does not parallel serum TSH levels. Of the initial enzyme activity 30-50% still remains when TSH secretion is suppressed by exogenous T4.