Insulin Represses Transcription of the Thyroid Stimulating Hormone β-Subunit Gene through Increased Recruitment of Nuclear Factor I

Abstract

Although the regulation of thyroid stimulating hormone ␤-subunit gene (TSH␤) has been intensively studied, the functions of transcription factors involved are not fully understood. The authors found that the ؊615/؊516 promoter region of the TSH␤ interacts specifically with nuclear proteins derived from pituitary tissue or from cultured thyrotroph cells. The actual binding site at the nucleotide level, as revealed by DNase I protection assay, includes the consensus sequence for nuclear factor I (NFI). RT-PCR analysis indicated that NFI-B expression is restricted to thyrotroph cells in the anterior pituitary. EMSA and ChIP analysis showed that NFI-B binds most efficiently to the ؊588/؊560 region of TSH␤ promoter. The forced expressions of NFI-B markedly reduced TSH␤ promoter activity and its mRNA expression. Furthermore, it was also shown that the ؊588/؊560 region is involved in the insulin-mediated repression of the TSH␤. It was of particular interest to observe that NFI-B was recruited to the ؊588/؊560 region of the TSH␤ promoter in an insulin-dependent manner. Taken together, this study provides new insights of the delicate regulations of energy metabolism and hormonal homeostasis.