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Titolo:
Distinct tissue-specific roles for thyroid hormone receptors beta and alpha 1 in regulation of type 1 deiodinase expression
Autore:
Amma, LL; Campos-Barros, A; Wang, ZD; Vennstrom, B; Forrest, D;
Indirizzi:
CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA CUNY Mt Sinai Sch Med New York NY USA 10029 Genet, New York, NY 10029 USA Karolinska Inst, CMB, Dev Biol Lab, S-17177 Stockholm, Sweden Karolinska Inst Stockholm Sweden S-17177 Lab, S-17177 Stockholm, Sweden
Titolo Testata:
MOLECULAR ENDOCRINOLOGY
fascicolo: 3, volume: 15, anno: 2001,
pagine: 467 - 475
SICI:
0888-8809(200103)15:3<467:DTRFTH>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
I IODOTHYRONINE 5'-DEIODINASE; RAT-KIDNEY; BINDING-CAPACITY; GENE-EXPRESSION; DEFICIENT MICE; TRIIODOTHYRONINE; ISOFORMS; RESISTANCE; TRANSCRIPTION; THYROXINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Forrest, D CUNY Mt Sinai Sch Med, Dept Human Genet, 1425 Madison Ave, New York, NY 10029 USA CUNY Mt Sinai Sch Med 1425 Madison Ave New York NY USA 10029 SA
Citazione:
L.L. Amma et al., "Distinct tissue-specific roles for thyroid hormone receptors beta and alpha 1 in regulation of type 1 deiodinase expression", MOL ENDOCR, 15(3), 2001, pp. 467-475

Abstract

Type 1 deiodinase (D1) metabolizes different forms of thyroid hormones to control levels of T-3, the active ligand for thyroid hormone receptors (TR). The D1 gene is itself T-3-inducible and here, the regulation of D1 expression by TR alpha1 and TR beta, which act as T-3-dependent transcription factors, was investigated in receptor-deficient mice. Liver and kidney D1 mRNAand activity levels were reduced in TR beta (-/-) but not TR alpha1(-/-) mice. Liver D1 remained weakly T-3 inducible in TR beta (-/-) mice whereas induction was abolished in double mutant TR alpha1(-/-)TR beta (-/-) mice. This indicates that TR beta is primarily responsible for regulating D1 expression whereas TR alpha1 has only a minor role. In kidney, despite the expression of both TR alpha1 and TR beta, regulation relied solely on TR beta, thus revealing a marked tissue restriction in TR isotype utilization. Although TR beta and TR alpha1 mediate similar functions in vitro, these results demonstrate differential roles in regulating D1 expression in vivo and suggest that tissue-specific factors and structural distinctions between TR isotypes contribute to functional specificity. Remarkably, there was an obligatory requirement for a TR, whether TR beta or TR alpha1, for any detectableD1 expression in liver. This suggests a novel paradigm of gene regulation in which the TR sets both basal expression and the spectrum of induced states. Physiologically, these findings suggest a critical role for TR beta in regulating the thyroid hormone status through D1-mediated metabolism.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 23:54:44