Thyroid hormone suppression of pituitary hormone gene expression.

Abstract

T3 suppression of TSH subunit gene transcription is an important step in maintaining thyroid hormone homeostasis, and recent investigations have increased our understanding of this process. Thyrotrope-specific proteins play a critical role in TSH subunit gene expression, and influence T3-mediated regulatory mechanisms. The structure and placement of the TSH gene TREs define suppressive regulation by T3, and this process is favored by the TR isoforms expressed in the pituitary. Elimination of TR beta function compromises the pituitary response to T3. TR beta 2, the isoform specifically expressed in pituitary and neural tissue, contains a transferable domain that both increases T3-independent gene transcription and enhances T3-suppressed transcription. The functional interaction of TR beta 2 with other regulatory proteins is distinct from that of other TR isoforms, and likely plays a critical role in pituitary physiology and in pituitary resistance to thyroid hormone. The development of novel thyrotrope cell lines will allow investigators to define new proteins and molecular mechanisms that distinguish negative from positive T3 transcriptional regulation.