Details

Autor(en) / Beteiligte

• Sadow, Peter M
• Chassande, Olivier
• Gauthier, Karine
• Samarut, Jacques
• Xu, Jianming
• O'Malley, Bert W
• Weiss, Roy E

Titel

Specificity of thyroid hormone receptor subtype and steroid receptor coactivator-1 on thyroid hormone action

Ist Teil von

• American journal of physiology: endocrinology and metabolism, 2003-01, Vol.284 (1), p.E36-E46

Ort / Verlag

United States: American Physiological Society

Erscheinungsjahr

2003

Quelle

MEDLINE

Beschreibungen/Notizen

• Departments of 1  Medicine and 2  Pathology, University of Chicago, Chicago, Illinois 60637; 3  Laboratoire de Biologie Moléculaire et Cellulaire de l'Ecole Normale Supérieure de Lyon, 69364 Lyon, France; and 4  Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030 Isoforms of the thyroid hormone receptor ( TR ) and TR genes mediate thyroid hormone action. How TR isoforms modulate tissue-specific thyroid hormone (TH) action remains largely unknown. The steroid receptor coactivator-1 (SRC-1) is among a group of transcriptional coactivator proteins that bind to TRs, along with other members of the nuclear receptor superfamily, and modulate the activity of genes regulated by TH. Mice deficient in SRC-1 possess decreased tissue responsiveness to TH and many steroid hormones; however, it is not known whether or not SRC-1-mediated activation of TH-regulated gene transcription in peripheral tissues, such as heart and liver, is TR isoform specific. We have generated mice deficient in TR and SRC-1, as well as in TR and SRC-1, and investigated thyroid function tests and effects of TH deprivation and TH treatment compared with wild-type (WT) mice or those deficient in either TR or SRC-1 alone. The data show that 1 ) in the absence of TR or TR , SRC-1 is important for normal growth; 2 ) SRC-1 modulates TR and TR effects on heart rate; 3 ) two new TR -dependent markers of TH action in the liver have been identified, osteopontin (upregulated) and glutathione S -transferase (downregulated); and 4 ) SRC-1 may mediate the hypersensitivity to TH seen in liver of TR -deficient mice. knockout; resistance to thyroid hormone; thyrotropin