Oestrogen action on thyroid progenitor cells: relevant for the pathogenesis of thyroid nodules?
Benign and malignant thyroid nodules are more prevalent in females than in men. 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 a target of oestrogen action. In thyroid stem/progenitor cells derived from nodular goitres the ability of 17beta-oestradiol to induce thyrosphere formation, the expression of oestrogen receptors and the effect of 17beta-oestradiol on growth, expression of marker of stem cells and thyroid differentiation (TSH receptor, thyroperoxidase, thyroglobulin, sodium iodide symporter expression) were analysed. 17beta-oestradiol induced thyrosphere formation, albeit to lower extent than other growth factors. Thyroid stem and progenitor cells expressed oestrogen receptor alpha and beta with an 8 time higher expression level of oestrogen receptor alpha mRNA compared to differentiated thyrocytes. 17beta-oestradiol was a potent stimulator of thyroid stem/ progenitor cell growth. In contrast, TSH-induced differentiation of progenitor cells, in particular the expression of the sodium iodide symporter, was significantly inhibited by 17beta-oestradiol.In conclusion, oestrogen stimulated growth and simultaneously inhibited differentiation of thyroid nodules 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 a selection of a progeny of growth-prone cells with a decreased differentiation. These cells may be the origin of hypo- or non-functioning thyroid nodules in females.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL GENE-Y GENE-Y GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
17beta-oestradiol sodium iodide 17beta-oestradiol oestrogen oestrogen Oestrogen sodium iodide symporter oestrogen receptors TSH receptor thyroperoxidase 17beta-oestradiol thyroglobulin sodium iodide symporter oestrogen receptor alpha and beta oestrogen receptor alpha sodium iodide 17beta-oestradiol oestrogen oestrogen oestrogen oestrogen 17beta-oestradiol oestrogen