Regulation of expression of thyroid hormone receptor isoforms and coactivators in liver and heart by thyroid hormone.
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 TR beta1 and TR alpha2 subtype expression is inversely related to TH levels and the regulation of TR beta expression is, in part, controlled by TR alpha. In the heart, the opposite is the case, regulation of TR alpha2 and TR beta1 isoform expression is directly related to TH levels and this regulation is primarily controlled by TR alpha. 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.
Sadow
Peter M
PM
Department of Medicine, Thyroid Study Unit, MC 3090, The University of Chicago, 5841 S. Maryland Ave, Chicago, IL 60637, USA.
Chassande
Olivier
O
Koo
Eugene K
EK
Gauthier
Karine
K
Samarut
Jacques
J
Xu
Jianming
J
O'Malley
Bert W
BW
Weiss
Roy E
RE
D000818:Animals; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2; D056921:Nuclear Receptor Coactivator 3; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics; D037042:Thyroid Hormone Receptors beta / Q000235:genetics; D013963:Thyroid Hormones / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
C498002:Ncoa2 protein, mouse; D051958:Nuclear Receptor Coactivator 2; D020033:Protein Isoforms; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D015534:Trans-Activators; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; C538867:Ncoa3 protein, mouse; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3