Regulation of expression of thyroid hormone receptor isoforms and coactivators in liver and heart by thyroid hormone

Abstract

Autoregulation of thyroid hormone (TH) receptors (TRs) is a mechanism whereby a cell can regulate its responsiveness to TH. Nuclear coactivators (NCoAs) modulate TH action and may also be important for regulation of TR expression. We have determined the effect of TH withdrawal and treatment on the expression of different isoforms of TR as well as expression of the NCoAs SRC-1, TIF-2 and SRC-3 using quantitative real time polymerase chain reaction. In order to identify the effect that each TR isoform exerts over the expression of the other, NCoA and TR transcripts were measured in liver and heart tissue from wild type mice or mice with deletion of either TR isoform or SRC-1 genes. In liver, regulation of TRβ1 and TRα2 subtype expression is inversely related to TH levels and the regulation of TRβ expression is, in part, controlled by TRα. In the heart, the opposite is the case, regulation of TRα2 and TRβ1 isoform expression is directly related to TH levels and this regulation is primarily controlled by TRα. Although NCoAs are, in general, increased in response to hypothyroidism or in states of TH resistance, SRC-1 specifically does not regulate TR isoform expression. We have demonstrated that TR isoforms and NCoAs are autoregulated transcription factors with tissue specificity.