Functional thyrotropin receptor expression in the pituitary folliculo-stellate cell line TtT/GF.
Thyrotropin secretion from the anterior pituitary is regulated mainly through TRH and thyroid hormones. Recent findings of a TSH receptor (TSHR) on folliculo-stellate (FS) cells in the human anterior pituitary indicate that TSH secretion might, in addition, be regulated in a paracrine manner via FS cells. In order to elucidate the physiological relevance of TSHR expression in FS cells we evaluated the effects of TSH on a murine FS cell line, TtT/GF. First, Western blot analysis confirmed the expression of TSHR protein in these cells. Second, three potential second messenger pathways were studied. Last, cDNA array hybridization was used to evaluate the effect of TSH on gene expression levels. TSH failed to induce either the adenylate cyclase/cAMP pathway, the phosphatidylinositol/calcium pathway, or the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 3 pathway. Most of the genes regulated by TSH were related to cell proliferation, cell differentiation, and apoptosis. Moreover, TSH induced STAT5a and TGFbeta2 expression. We report that TtT/GF cells express a functional TSHR that is not coupled to cAMP nor IP (3) but probably signals through the JAK/STAT5a pathway. Functional TSHR expression in this cell line offers an in vitro model to study the role of TSHR in FS cells.
Brokken
L J S
LJ
Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Leon.Brokken@utu.fi
Bakker
O
O
Wiersinga
W M
WM
Prummel
M F
MF
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D051379:Mice; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D011989:Receptors, Thyrotropin / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D015290:Second Messenger Systems; D015398:Signal Transduction; D013972:Thyrotropin / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D011989:Receptors, Thyrotropin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D015544:Inositol 1,4,5-Trisphosphate; D013972:Thyrotropin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases