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 investigated a possible role of estrogen on thyroid follicular cell growth using rat FRTL-5 thyroid follicular cells as a model. Estrogen receptor-alpha (ERalpha) 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 was transfected into FRTL-5 cells to test the functionality of the endogenous ERs. Estradiol increased the activity of the reporter gene, and the antagonist, ICI182780, inhibited ER-dependent transcription. To extend this analysis, we examined the effect of estradiol on FRTL-5 cell growth. Estradiol increased FRTL-5 cell growth in a time- and concentration-dependent manner in 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 sodium/iodide symporter (NIS) was assessed as a potential target of estrogen action. 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 that enhance cell growth and inhibit expression of the NIS. The demonstration of a direct effect of estradiol on thyroid follicular cells raises the possibility that it may play a role in the sexually dimorphic prevalence of goiter.
Furlanetto
T W
TW
Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Nguyen
L Q
LQ
Jameson
J L
JL
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects*; D008565:Membrane Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters; D013961:Thyroid Gland / Q000737:chemistry / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D000099209:Sodium-Iodide Symporters
D002352:Carrier Proteins; D004958:Estradiol; D004965:Estrogen Antagonists; D000077267:Fulvestrant; D008565:Membrane Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D027981:Symporters; D013972:Thyrotropin; D000099209:Sodium-Iodide Symporters