Polychronakos C, Guyda H J, Patel B, Posner B I
Endocrinology. 1986 Sep;119(3):1204-9. doi: 10.1210/endo-119-3-1204.
We have observed that membranes isolated from rat thyroids contain receptors for the insulin-like growth factors (IGF). As IGFs are known to be important mediators of tissue growth, we conducted this study to determine whether modulation of thyroid IGF receptors might be involved in TSH-stimulated hyperplasia. A substantial increase in both the weight of the thyroid and its DNA content was observed within 2 days of exposing adult male rats to 0.1% propylthiouracil (PTU) in their drinking water. Serum T4 reached unmeasurable levels and serum TSH rose 3-fold over control by the tenth day of treatment. [125I]Iodo-human(h)IGF-II binding to membranes isolated from hyperplastic glands was significantly higher than control beginning at 2 days. A maximum was reached after 5 days (13.3 +/- 0.8%/25 micrograms protein vs. a control level of 6.7 +/- 0.7%, mean +/- SEM). The increase had disappeared by 15 days of PTU exposure, paralleling the drastic fall in the growth rate of the glands. This increase in binding was specific for the thyroid, as it was not seen in other organs. In both treated and control animals, the receptor involved was shown to be type II by preferential binding to IGF-II, lack of interaction with insulin, and molecular sizing. The observed increase in binding could be accounted for by an increase in receptor site number, the affinity remaining essentially the same. We conclude that the TSH-stimulated hyperplasia of the rat thyroid, induced by PTU, is associated with an increase in the binding sites of the type II IGF receptor. This observation raises the possibility that modulation of this receptor may play a role in the mediation of the mitogenic effect of TSH on the thyroid gland.
我们观察到，从大鼠甲状腺分离出的细胞膜含有胰岛素样生长因子（IGF）受体。由于已知IGF是组织生长的重要介质，我们开展了本研究，以确定甲状腺IGF受体的调节是否可能参与促甲状腺激素（TSH）刺激的增生。在成年雄性大鼠饮用水中加入0.1%丙硫氧嘧啶（PTU）后2天内，观察到甲状腺重量及其DNA含量均显著增加。治疗第10天时，血清甲状腺素（T4）降至无法检测的水平，血清TSH比对照组升高了3倍。从第2天开始，[125I]碘人（h）IGF-II与从增生腺体分离出的细胞膜的结合显著高于对照组。5天后达到最大值（13.3±0.8%/25微克蛋白质，而对照组水平为6.7±0.7%，均值±标准误）。PTU暴露15天时，这种增加消失，与腺体生长速率的急剧下降相一致。这种结合增加是甲状腺特有的，在其他器官中未观察到。在治疗组和对照组动物中，通过对IGF-II的优先结合、与胰岛素缺乏相互作用以及分子大小测定，表明所涉及的受体为II型。观察到的结合增加可能是由于受体位点数量增加，亲和力基本保持不变。我们得出结论，PTU诱导的大鼠甲状腺TSH刺激增生与II型IGF受体结合位点增加有关。这一观察结果提出了一种可能性，即该受体的调节可能在TSH对甲状腺的促有丝分裂作用的介导中发挥作用。
