Alterations in thyrotropin (TSH) binding in iodine-deficient rats

Abstract

Thyrotropin (TSH) is thought to stimulate thyroid activity and growth by binding to TSH receptors on thyroid plasma membranes. Iodine depletion has been shown to increase the sensitivity of the thyroid to the goitrogenic effects of TSH. The present investigation was performed to determine if chronic iodine depletion altered either the number or the affinity of TSH receptor sites in the thyroid. Six paired experiments were performed comparing the binding of 125I-labeled bovine TSH to a particulate fraction of thyroid from male Sprague-Dawley rats that had received regular (C) or low iodine diet (LID) for 3 to 7 months. The number of TSH receptors and the association constants of these receptors were calculated from Scatchard plots and binding was compared with glandular concentrations of DNA, RNA, protein, plasma membrane markers (5′-nucleotidase, Mg 2+ ATPase, Na +, K + ATPase), and per thyroid gland. (1) The weights of all animals were initially similar but after 3 to 7 months the LID group (638 ± 139 g (mean ± 1 SD)) was heavier than the C group (544 ± 45 g ( P < .01)). (2) Serum TSH concentrations in the LID group (5231 ± 547 ng/ml) were higher than those in the C group (850 ± 221 ng/ml) ( P < .005). (3) Thyroid weight, thyroid weight per animal weight, DNA, RNA, total protein, Mg 2+ ATPase, Na +, K + ATPase, and 5′-nucleotidase were all increased in the LID group ( P < .005). Histological examination demonstrated that the thyroid enlargement was primarily due to an increase in number of follicle cells, or hyperplasia. (4) The concentration of TSH receptors (maximum binding capacity) per DNA content was similar in the C and LID groups. (5) The concentration of TSH receptors per plasma membrane marker decreased in the LID group ( P < .01) primarily because of the large increase in amount of plasma membrane. (6) The total number of TSH receptors per thyroid gland or TSH receptor content increased from 0.52 ± 0.16 × 10 14 in the C group to 2.27 ± 0.79 × 10 14 in the iodine-deficient animals ( P < .001), and the association constant in these animals (1.28 ± .27 × 10 8 M −1) was also higher than that in the C group (0.68 ± 0.16 × 10 8 M −1) ( P < .001). Thus, chronically iodine-deficient rats developed increased serum TSH concentrations and enlarged hyperplastic thyroid glands. Although the number of TSH receptors per DNA or cell did not change in the respective groups, the TSH receptor content and the association constant of these receptors for TSH in the thyroid gland of the iodine-deficient animals increased. It therefore appears that increased serum TSH concentrations in iodine-deficient rats exerts a positive regulatory effect on its own receptors and that alterations in serum TSH level modulate the TSH receptor. Whether this effect is due to a direct effect of TSH on the TSH receptor or an indirect effect secondary to thyroid growth is unknown.