Sensitivity of thyroid gland growth to thyroid stimulating hormone (TSH) in rats treated with antithyroid drugs.

Antithyroid drugs and phenobarbital (PB) have been shown to promote thyroid tumors in rats. It has been proposed that increased thyroid-stimulating hormone (TSH) mediates the thyroid tumor-promoting effect of antithyroid drugs and PB, and is increased because of decreased thyroxine (T4) concentration. However, PB is much less effective than antithyroid drugs at increasing TSH. It has been proposed that small increases in serum TSH produced by PB treatment is sufficient to promote thyroid tumors. However, the level to which TSH must be increased to stimulate the thyroid gland has not been reported. Therefore, we have examined the effect of increasing serum TSH concentration on thyroid growth by measuring thyroid gland weight and thyroid follicular cell proliferation. Serum TSH concentrations were increased by feeding rats various concentrations of propylthiouracil (PTU) or methimazole (MMI) for 21 days. Serum total T4, free T4, total T3 (triiodothyronine), free T3, and TSH concentrations were measured by radioimmunoassay. Thyroid follicular cell proliferation was measured by autoradiography and expressed as a labeling index (LI). PTU and MMI treatments reduced total and free T4 more than 95% by day 21, whereas total and free T3 were reduced 60%. TSH, thyroid follicular cell proliferation and thyroid weight were increased 560%, 1400%, and 200%, respectively, by day 21. TSH was significantly correlated with thyroid weight and LI. Moderate increases in serum TSH of between 10 and 20 ng/ml increased the number of proliferating thyroid follicular cells, but had no effect on thyroid weight. These results support that small increases in serum TSH can be sufficient to stimulate thyroid follicular cell proliferation. Furthermore, thyroid follicular cell proliferation may be more useful than thyroid weight alone for assessing alterations in thyroid growth in rats treated with chemicals that produce only small to moderate increases in serum TSH.