Peter H J, Gerber H, Studer H, Smeds S
J Clin Invest. 1985 Nov;76(5):1992-2002. doi: 10.1172/JCI112199.
Functional and morphologic heterogeneity of human multinodular goiters was investigated in 300 samples from "cold" and "hot" regions of 20 goiters transplanted onto nude mice. Transplants were labeled with [3H]thymidine and radioiodine, while the host's thyroid-stimulating hormone (TSH) secretion was either stimulated or suppressed. Proliferation and function of follicular cells were assessed in whole follicles reconstructed from autoradiographs of serial sections. Hot transplants had a higher autonomous iodine uptake than those of cold tissue in TSH-suppressed hosts. Functional autonomy widely varied among the follicles, but even more so among individual cells. Hot grafts differed from cold ones only by a comparatively larger fraction of autonomous cells. Intercellular differences of iodinating activity were not abolished by TSH. Grafts faithfully reproduced the individual growth pattern of the original tissue. Between 0.5% and 7% of all follicular cells replicated despite suppression of TSH. Up to 70% of these cells were clustered, forming scattered foci of autonomously growing tissue. Other cells only started replicating after long-term TSH stimulation. Thus, goiters contained subsets of cells with high and others with low growth response. Progenies of replicating cells remained clustered, sometimes budding outwards to form new follicles. Autonomy of growth and autonomy of function are independent traits of epithelial cells. Epithelial cells have their individual growth pattern, replication rate, and functional capacity. These traits are passed on from a mother cell to its progeny during follicle neogenesis. To this main mechanism accounting for the morphologic and functional heterogeneity of human goiters, inheritable modifications of gene expression must probably be added.
对移植到裸鼠身上的20个甲状腺肿的300个样本进行了研究，以探讨人类多结节性甲状腺肿的功能和形态异质性。这些移植样本来自“冷”区和“热”区的甲状腺肿，用[3H]胸腺嘧啶核苷和放射性碘进行标记，同时对宿主的促甲状腺激素（TSH）分泌进行刺激或抑制。通过对连续切片的放射自显影片重建的整个滤泡来评估滤泡细胞的增殖和功能。在TSH抑制的宿主中，热移植样本的自主碘摄取高于冷组织。滤泡之间的功能自主性差异很大，但单个细胞之间的差异更大。热移植样本与冷移植样本的区别仅在于自主细胞的比例相对较大。TSH并不能消除碘化活性的细胞间差异。移植样本忠实地再现了原始组织的个体生长模式。尽管TSH受到抑制，但所有滤泡细胞中有0.5%至7%仍在复制。其中高达70%的细胞聚集在一起，形成自主生长组织的散在病灶。其他细胞只有在长期TSH刺激后才开始复制。因此，甲状腺肿包含生长反应高和低的细胞亚群。复制细胞的后代仍然聚集在一起，有时向外芽生形成新的滤泡。生长自主性和功能自主性是上皮细胞的独立特征。上皮细胞有其个体生长模式、复制速率和功能能力。这些特征在滤泡新生过程中从母细胞传递给后代。对于人类甲状腺肿形态和功能异质性的主要机制，可能还必须加上基因表达的可遗传修饰。
