Role of the thyroid-stimulating hormone receptor signaling in development and differentiation of the thyroid gland.
The thyroid-stimulating hormone/thyrotropin (TSH) is the most relevant hormone in the control of thyroid gland physiology in adulthood. TSH effects on the thyroid gland are mediated by the interaction with a specific TSH receptor (TSHR). We studied the role of TSHTSHR signaling on gland morphogenesis and differentiation in the mouse embryo using mouse lines deprived either of TSH (pit(dw)pit(dw)) or of a functional TSHR (tshr(hyt)tshr(hyt) and TSHR-knockout lines). The results reported here show that in the absence of either TSH or a functional TSHR, the thyroid gland develops to a normal size, whereas the expression of thyroperoxidase and the sodium/iodide symporter are reduced greatly. Conversely, no relevant changes are detected in the amounts of thyroglobulin and the thyroid-enriched transcription factors TTF-1, TTF-2, and Pax8. These data suggest that the major role of the TSH/TSHR pathway is in controlling genes involved in iodide metabolism such as sodium/iodide symporter and thyroperoxidase. Furthermore, our data indicate that in embryonic life TSH does not play an equivalent role in controlling gland growth as in the adult thyroid.
Postiglione
M P
MP
Laboratory of Biochemistry and Molecular Biology, Stazione Zoologica A. Dohrn, Villa Comunale, 80121 Naples, Italy.
Parlato
R
R
Rodriguez-Mallon
A
A
Rosica
A
A
Mithbaokar
P
P
Maresca
M
M
Marians
R C
RC
Davies
T F
TF
Zannini
M S
MS
De Felice
M
M
Di Lauro
R
R
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005865:Gestational Age; D006801:Humans; D007037:Hypothyroidism / Q000196:embryology / Q000235:genetics; D007453:Iodide Peroxidase / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D009929:Organ Size; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011989:Receptors, Thyrotropin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics; D013954:Thyroglobulin / Q000096:biosynthesis / Q000235:genetics; D013961:Thyroid Gland / Q000196:embryology* / Q000254:growth & development / Q000473:pathology; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000099209:Sodium-Iodide Symporters
D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D007453:Iodide Peroxidase; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D027981:Symporters; D013954:Thyroglobulin; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin; D015534:Trans-Activators; D014157:Transcription Factors; D000099209:Sodium-Iodide Symporters; C106894:FOXE1 protein, human; C000614412:NKX2-1 protein, human; C000614414:Nkx2-1 protein, mouse; C083325:PAX8 protein, human; C499496:Pax8 protein, mouse