Regulation of hepatocyte thyroxine 5'-deiodinase by T3 and nuclear receptor coactivators as a model of the sick euthyroid syndrome.
J Biol Chem
; 275(49): 38296-301, 2000 Dec 08.
Article
em En
| MEDLINE
| ID: mdl-10995750
ABSTRACT
The syndrome of nonthyroidal illness, also known as the sick euthyroid syndrome, is characterized by a low plasma T3 and an "inappropriately normal" plasma thyrotropin in the absence of intrinsic disease of the hypothalamic-pituitary-thyroid axis. The syndrome is due in part to decreased activity of type I iodothyronine 5'-deiodinase (5' D-I), the hepatic enzyme that converts thyroxine to T3 and that is induced at the transcriptional level by T3. The hypothesis tested is that cytokines decrease T3 induction of 5' D-I, resulting in decreased T3 production and hence a further decrease in 5' D-I. The proposed mechanism is competition for limiting amounts of nuclear receptor coactivators between the 5' D-I promoter and the promoters of cytokine-induced genes. Using primary cultures of rat hepatocytes, we demonstrate that interleukins 1 and 6 inhibit the T3 induction of 5' D-I RNA and enzyme activity. This effect is at the level of transcription and can be partially overcome by exogenous steroid receptor coactivator-1 (SRC-1). The physical mass of endogenous SRC-1 is not affected by cytokine exposure, and exogenous SRC-1 does not affect 5' D-I in the absence of cytokines. The data support the hypothesis that cytokine-induced competition for limiting amounts of coactivators decreases hepatic 5' D-I expression, contributing to the etiology of the sick euthyroid syndrome.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Tri-Iodotironina
/
Síndromes do Eutireóideo Doente
/
Regulação Enzimológica da Expressão Gênica
/
Citocinas
/
Receptores Citoplasmáticos e Nucleares
/
Hepatócitos
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Iodeto Peroxidase
/
Fígado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos