Langer R, Burzler C, Bechtner G, Gärtner R
Department of Pathology, Technische Universität München, Munich, Germany.
Exp Clin Endocrinol Diabetes. 2003 Sep;111(6):325-9. doi: 10.1055/s-2003-42721.
Iodine induced thyroid involution is caused by apoptosis rather than necrosis. This effect of iodide on apoptosis of thyroid epithelial cells may be not a direct one but mediated by iodinated derivatives i.e. of polyunsaturated fatty acids, especially of iodolactones, which have previously shown to inhibit thyroid cell proliferation. We studied the influence on apoptosis of iodide (2 microM and 20 microM) and iodolactone (0.05 microM and 0.5 microM), with and without TSH (1 mU/ml), using a well characterized ex vivo- culture system of intact porcine thyroid follicles in three-dimensional culture. Apoptosis and necrosis was evaluated by electron-microscopy. Stimulation with 2 and 20 microM iodide rapidly induced a rate of apoptosis (4 - 6 %) comparable to about 40-fold lower doses of delta-iodolactone (0.05 microM and 0.5 microM). Addition of TSH (1 mU/ml) caused a slight but not significant further increase of the incidence of apoptotic cells. The rate of necrotic thyroid epithelial cells (1 - 2 %) was similar in all experiments. As delta-iodolactone in very low concentrations--comparable to iodide in higher concentrations--not only inhibits growth but also induces apoptosis, it has to be supposed that the effect of iodide is mediated by this iodinated compound. However, further experiments are necessary to confirm this hypothesis. In addition it could be demonstrated, that apoptosis is a very rapid and limited process in intact follicles. This also may explain, why iodine supplementation even in high doses does not lead to thyroid atrophy but only normalisation of thyroid size. These results confirm that apoptosis is an important regulated and limited mechanism in goiter involution.
碘诱导的甲状腺 involution 是由凋亡而非坏死引起的。碘化物对甲状腺上皮细胞凋亡的这种作用可能不是直接的，而是由碘化衍生物介导的，即多不饱和脂肪酸的碘化衍生物，尤其是碘内酯，此前已证明其可抑制甲状腺细胞增殖。我们使用三维培养中完整猪甲状腺滤泡的特征明确的离体培养系统，研究了碘化物（2 microM 和 20 microM）和碘内酯（0.05 microM 和 0.5 microM）在有和没有促甲状腺激素（1 mU/ml）的情况下对凋亡的影响。通过电子显微镜评估凋亡和坏死情况。用 2 和 20 microM 碘化物刺激迅速诱导凋亡率（4 - 6%），这与低约 40 倍剂量的δ-碘内酯（0.05 microM 和 0.5 microM）相当。添加促甲状腺激素（1 mU/ml）导致凋亡细胞发生率略有但不显著的进一步增加。在所有实验中，坏死的甲状腺上皮细胞率（1 - 2%）相似。由于极低浓度的δ-碘内酯——与较高浓度的碘化物相当——不仅抑制生长，还诱导凋亡，因此可以推测碘化物的作用是由这种碘化化合物介导的。然而，需要进一步的实验来证实这一假设。此外，可以证明，凋亡在完整滤泡中是一个非常迅速且有限的过程。这也可以解释为什么即使高剂量补充碘也不会导致甲状腺萎缩，而只会使甲状腺大小恢复正常。这些结果证实凋亡是甲状腺肿 involution 中一种重要的受调控且有限的机制。
