Morgan Sarah J, Neumann Susanne, Marcus-Samuels Bernice, Gershengorn Marvin C
Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD , USA.
Front Endocrinol (Lausanne). 2016 Dec 26;7:168. doi: 10.3389/fendo.2016.00168. eCollection 2016.
Although TSH has been suggested to be a proliferative agent for thyrocytes, the effect of TSH on human thyroid cells remains controversial. In particular, most of the reported studies relied primarily on changes in DNA synthesis but have not included measurement of the number of cells. We argue that only a direct count of cell number, demonstrating classical exponential expansion, serves as a valid measurement of proliferation. Thus, although some data support TSH as a proliferative agent, most do not provide conclusive evidence. To generate conclusive evidence with regard to a proliferative effect of TSH in human thyrocytes, we performed various experiments using primary cultures of human thyrocytes. In contrast to previous reports, TSH [±insulin-like growth factor 1 (IGF-1)] did not induce proliferation of thyrocytes under a variety of different conditions. However, TSH/IGF-1 cotreatment did upregulate thyroid-specific gene expression including and in a manner consistent with cellular differentiation. Evidence for a proliferative effect of TSH has been used to inform the American Thyroid Association's guidelines for the management of thyroid cancer patients, which include TSH suppression. While these recommendations are admittedly based on low- to moderate-quality evidence, TSH suppression is still widely used. We present data that question the consensus view that TSH promotes proliferation of human thyrocytes (upon which the American Thyroid Association's guidelines are based) and suggest that additional studies, including randomized controlled trials, are warranted to address this important clinical question.
尽管促甲状腺激素（TSH）被认为是甲状腺细胞的增殖因子，但TSH对人甲状腺细胞的作用仍存在争议。特别是，大多数已报道的研究主要依赖于DNA合成的变化，而未包括细胞数量的测量。我们认为，只有直接计数细胞数量并证明经典的指数增长，才能作为增殖的有效测量方法。因此，尽管一些数据支持TSH作为增殖因子，但大多数数据并未提供确凿的证据。为了获得关于TSH对人甲状腺细胞增殖作用的确凿证据，我们使用人甲状腺细胞原代培养进行了各种实验。与先前的报道相反，在各种不同条件下，TSH[±胰岛素样生长因子1（IGF-1）]并未诱导甲状腺细胞增殖。然而，TSH/IGF-1联合处理确实以上调甲状腺特异性基因表达，包括 和 ，其方式与细胞分化一致。TSH增殖作用的证据已被用于为美国甲状腺协会甲状腺癌患者管理指南提供参考，其中包括TSH抑制。虽然这些建议诚然基于低至中等质量的证据，但TSH抑制仍被广泛使用。我们提供的数据对TSH促进人甲状腺细胞增殖的共识观点（美国甲状腺协会指南所基于的观点）提出了质疑，并建议进行更多研究，包括随机对照试验，以解决这一重要的临床问题。
