Thyroid hormone regulation of the human thyrotropin β-subunit gene (TSHβ) was examined in a human embryonal cell line (293). Transient expression studies were performed with chimeric plasmids containing the reporter gene, chloramphenicol acetyltransferase. Sequences in the first exon between +9 and +37 base pairs (bp) enhanced gene expression from the human TSHβ promoter in the absence of thyroid hormone as well as mediated a concentration-dependent triiodothyronine (L-T3) decrease in gene expression. Thyroid hormone inhibition of expression was also conferred to the herpex simplex virus thymidine kinase promoter by inserting +3 to +37 bp of the human TSHβ gene downstream from the start of transcription. Primer extension analysis of RNA from transfected cell cultures revealed accurate transcription initiation in only those constructs which contained sequences between +9 and +37 bp. Moreover, RNA analysis confirmed that L-T3 inhibition of chloramphenicol acetyltransferase activity from chimeric pTSHβCAT constructs occurred at a pretranslational level. In addition, a nuclear thyroid hormone receptor, c-erbA-β, bound to this region in an avidin-biotin DNA binding assay. These data suggest that L-T3, bound to its receptor, may inhibit human TSHβ expression by interfering with an element that functions to enhance gene expression.
|Original language||English (US)|
|Number of pages||4|
|Journal||Journal of Biological Chemistry|
|State||Published - Jan 1 1989|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology