Division of Endocrinology, Department of Medicine, St Hedwig Hospital, Berlin, Germany.
J Endocrinol. 2013 Jun 1;218(1):125-33. doi: 10.1530/JOE-13-0029. Print 2013 Jul.
Benign and malignant thyroid nodules are more prevalent in females than in males. Experimental data suggest that the proliferative effect of oestrogen rather than polymorphisms is responsible for this gender difference. This study analysed whether both differentiated thyroid cells and thyroid stem and progenitor cells are targets of oestrogen action. In thyroid stem/progenitor cells derived from nodular goitres, the ability of 17β-oestradiol (E₂) to induce the formation of thyrospheres and the expression of oestrogen receptors (ERs) and the effect of E₂ on the growth and expression of markers of stem cells and thyroid differentiation (TSH receptor, thyroperoxidase, thyroglobulin and sodium iodide symporter (NIS)) were analysed. E₂ induced thyrosphere formation, albeit to a lower extent than other growth factors. Thyroid stem and progenitor cells expressed ERα (ESR1) and ERβ (ESR2) with eight times higher expression levels of ERα mRNA compared with the differentiated thyrocytes. E₂ was a potent stimulator of the growth of thyroid stem/progenitor cells. In contrast, TSH-induced differentiation of progenitor cells, in particular, the expression of NIS, was significantly inhibited by E₂. In conclusion, oestrogen stimulated the growth and simultaneously inhibited the differentiation of thyroid nodule-derived stem/progenitor cells. From these data and based on the concept of cellular heterogeneity, we hypothesize a supportive role of oestrogen in the propagation of thyroid stem/progenitor cells leading to the selection of a progeny of growth-prone cells with a decreased differentiation. These cells may be the origin of hypofunctioning or non-functioning thyroid nodules in females.
良性和恶性甲状腺结节在女性中比在男性中更为常见。实验数据表明，雌激素的增殖作用而不是多态性是导致这种性别差异的原因。本研究分析了雌激素作用的靶细胞是否既包括分化的甲状腺细胞，也包括甲状腺干细胞和祖细胞。在来源于结节性甲状腺肿的甲状腺干细胞/祖细胞中，分析了 17β-雌二醇（E₂）诱导形成甲状腺球体以及雌激素受体（ERs）表达的能力，以及 E₂对干细胞和甲状腺分化标志物（促甲状腺激素受体、甲状腺过氧化物酶、甲状腺球蛋白和钠碘同向转运体（NIS））的生长和表达的影响。E₂诱导了甲状腺球体的形成，但程度低于其他生长因子。甲状腺干细胞和祖细胞表达 ERα（ESR1）和 ERβ（ESR2），与分化的甲状腺细胞相比，ERα mRNA 的表达水平高 8 倍。E₂是甲状腺干细胞/祖细胞生长的有效刺激物。相比之下，促甲状腺激素诱导的祖细胞分化，特别是 NIS 的表达，被 E₂显著抑制。总之，雌激素刺激了甲状腺结节来源的干细胞/祖细胞的生长，同时抑制了其分化。基于这些数据和细胞异质性的概念，我们假设雌激素在甲状腺干细胞/祖细胞的增殖中起支持作用，导致增殖倾向细胞的后代选择减少，分化能力降低。这些细胞可能是女性功能性或非功能性甲状腺结节的起源。
