Thyroid hormone exerts site-specific effects on SRC-1 and NCoR expression selectively in the neonatal rat brain.
Thyroid hormone receptors (TRs) are ligand-gated transcription factors. Recently, many coregulator proteins have been identified that interact with steroid/TRs and are required for the activation or repression of hormone sensitive genes. We tested whether steroid receptor coactivator-1 (SRC-1) and nuclear corepressor (N-CoR) expression is altered by hypothyroidism in rat brains on gestational day 16 and postnatal day 15. We found that both SRC-1 and N-CoR mRNA levels were decreased in the cortex and dentate gyrus of 6-n-propyl-2 thiouracil treated rats only on P15, while mRNA levels for both genes were increased in the same CA3 region of the brains. These findings do not support the idea that cofactors are involved in the compensatory mechanisms for conserving TH action, but they do suggest that hypothyroidism affects the responsiveness of tissues to steroid hormones by altering the expression of necessary cofactors.
Iannacone
Eric A
EA
Biology Department and Molecular and Cellular Biology Program, Morrill Science Center, University of Massachusetts, Amherst, MA 01003, USA.
Yan
Arthur W
AW
Gauger
Kelly J
KJ
Dowling
Amy L S
AL
Zoeller
R Thomas
RT
D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000032:analysis / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D051548:Histone Acetyltransferases; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D051579:Neurogranin; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1; D056920:Nuclear Receptor Coactivator 1; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011987:Receptors, Steroid / Q000378:metabolism*; D012097:Repressor Proteins / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000097:blood / Q000494:pharmacology*; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*
D002148:Calmodulin-Binding Proteins; C539129:Ncor1 protein, rat; D009419:Nerve Tissue Proteins; C496651:Nrgn protein, rat; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D012333:RNA, Messenger; D011987:Receptors, Steroid; D012097:Repressor Proteins; D013963:Thyroid Hormones; D014157:Transcription Factors; D051579:Neurogranin; D051548:Histone Acetyltransferases; D056920:Nuclear Receptor Coactivator 1