[Transcriptional repression of the TRH gene]

The synthesis and secretion of thyroid hormones (TH: T3, T4) must be strictly regulated. TH act on their own production via a negative feedback system. The synthesis of thyrotropin-releasing hormone (TRH), produced in the hypothalamus, and thyrotropin (TSH) in the pituitary is inhibited at the transcriptional level by TH. TRH and TSH stimulate production of TH. An outstanding, still open, question is the molecular basis of T3-dependent transcription repression of TRH and TSH genes. However, some regulatory components have been identified, with the b-TH receptor (TRb) playing a specific regulatory role (versus TRa) in the negative feedback effects of T3 on production of TRH and TSH. Moreover, the N-terminus of TRb is known to be a key element in this regulation. A hypothesis to explain this isoform specificity could be that TRb and TRa interact differentially with transcriptional comodulators. Thus, it is critical to characterize these comodulators and to analyse their contribution to the transcription regulation of TRH.