Tw. Furlanetto et al., Estradiol increases proliferation and down-regulates the sodium/iodide symporter gene in FRTL-5 cells, ENDOCRINOL, 140(12), 1999, pp. 5705-5711
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.