Modulation of thyroid-specific gene expression in normal and nodular human thyroid tissues from adults: an in vivo effect of thyrotropin.
BACKGROUND
Evidence from in vitro studies or animal models has shown that TSH affects thyrocytes by thyroid-specific expression modulation.


OBJECTIVE
The objective of our study was to analyze the role of TSH in human thyroid gene expression in vivo.


METHODS
Thirty-nine normal thyroid tissues were collected at the same center.


METHODS
Patients were divided into two groups based on serum TSH levels: 17 with normal TSH levels (1-4 mU/liter; group 1) and 22 with TSH levels below 0.5 mU/liter (group 2).


METHODS
Group 2 underwent thyroidectomy after suppressive L-T4 therapy.


METHODS
mRNA levels of thyroid genes such as sodium/iodide symporter (NIS), apical iodide transporter, pendrin, thyroglobulin, thyroperoxidase, TSH receptor, paired box transcription factor 8, and thyroid transcription factor-1 were evaluated by quantitative PCR.


RESULTS
The reduction of TSH stimulation causes decreases in NIS and apical iodide transporter gene expression in normal tissues and more limited reductions in thyroglobulin, thyroperoxidase, and paired box transcription factor 8, but it has no significant effect on TSH receptor, pendrin, or thyroid transcription factor-1. Comparison of NIS levels in normal and nodular tissues from the same patient confirmed that it is differentially expressed in nodules only in the presence of normal TSH (P < 0.01). In patients with suppressed TSH, nodular NIS levels were similar to those in normal tissues.


CONCLUSIONS
Our data represent the first demonstration in human thyroid tissues that TSH contributes to the regulation of thyrocyte differentiation by modulating thyroid gene levels. It exerts a particularly important effect on the transcription of NIS, which becomes very low after prolonged TSH suppression.
Bruno
Rocco
R
Ospedale di Tinchi-Pisticci, Matera, Italy.
Ferretti
Elisabetta
E
Tosi
Emanuele
E
Arturi
Franco
F
Giannasio
Paolo
P
Mattei
Tiziana
T
Scipioni
Angela
A
Presta
Ivan
I
Morisi
Roberta
R
Gulino
Alberto
A
Filetti
Sebastiano
S
Russo
Diego
D
D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007453:Iodide Peroxidase / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger / Q000096:biosynthesis; D011989:Receptors, Thyrotropin / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000076988:Sulfate Transporters; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics; D013954:Thyroglobulin / Q000096:biosynthesis / Q000235:genetics; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D013965:Thyroidectomy; D013972:Thyrotropin / Q000494:pharmacology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000099209:Sodium-Iodide Symporters
D004268:DNA-Binding Proteins; D007453:Iodide Peroxidase; D026901:Membrane Transport Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D000076988:Sulfate Transporters; D027981:Symporters; D013954:Thyroglobulin; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin; D015534:Trans-Activators; D014157:Transcription Factors; D000099209:Sodium-Iodide Symporters; C000614412:NKX2-1 protein, human; C083325:PAX8 protein, human; C439529:SLC26A6 protein, human