Estradiol increases proliferation and down-regulates the sodium/iodide symporter gene in FRTL-5 cells

Goiter (increased thyroid gland size) is more prevalent in women than men, even in areas where iodine levels in the diet are sufficient. We investigat ed a possible role of estrogen on thyroid follicular cell growth using rat FRTL-5 thyroid follicular cells as a model. Estrogen receptor-alpha (ER alp ha) messenger RNA was present in FRTL-5 cells using a RT-PCR assay and was confirmed by Western blot analysis. An estrogen-responsive reporter gene wa s transfected into FRTL-5 cells to test the functionality of the endogenous ERs. Estradiol increased the activity of the reporter gene, and the antago nist, ICI182780, inhibited ER-dependent transcription. To extend this analy sis, we examined the effect of estradiol on FRTL-5 cell growth. Estradiol i ncreased FRTL-5 cell growth in a time- and concentration-dependent manner i n either the absence or presence of TSH. Because iodine is known to inhibit thyroid cell growth, the effect of estradiol on the expression of the sodi um/iodide symporter (NIS) was assessed as a potential target of estrogen ac tion. Estradiol blocked TSH-induced NIS expression, and treatment of cells with estradiol and ICI182780 restored TSH-induced NIS expression to normal levels. These data demonstrate that FRTL-5 cells contain functional ERs tha t enhance cell growth and inhibit expression of the NIS. The demonstration of a direct effect of estradiol on thyroid follicular cells raises the poss ibility that it may play a role in the sexually dimorphic prevalence of goi ter.