Thyroid hormone-sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform-specific

M. O. Ribeiro, S. D. Carvalho, J. J. Schultz, G. Chiellini, T. S. Scanlan, A. C. Bianco, G. A. Brent

Research output: Contribution to journalArticle

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Abstract

In newborns and small mammals, cold-induced adaptive (or nonshivering) thermogenesis is produced primarily in brown adipose tissue (BAT). Heat production is stimulated by the sympathetic nervous system, but it has an absolute requirement for thyroid hormone. We used the thyroid hormone receptor-β-selective (TR-β-selective) ligand, GC-1, to determine by a pharmacological approach whether adaptive thermogenesis was TR isoform-specific. Hypothyroid mice were treated for 10 days with varying doses of T3 or GC-1. The level of uncoupling protein 1 (UCP1), the key thermogenic protein in BAT, was restored by either T3 or GC-1 treatment. However, whereas interscapular BAT in T3-treated mice showed a 3.0°C elevation upon infusion of norepinephrine, indicating normal thermogenesis, the temperature did not increase (<0.5°C) in GC-1-treated mice. When exposed to cold (4° C), GC-1-treated mice also failed to maintain core body temperature and had reduced stimulation of BAT UCP1 mRNA, indicating impaired adrenergic responsiveness. Brown adipocytes isolated from hypothyroid mice replaced with T3, but not from those replaced with GC-1, had normal cAMP production in response to adrenergic stimulation in vitro. We conclude that two distinct thyroid-dependent pathways, stimulation of UCP1 and augmentation of adrenergic responsiveness, are mediated by different TR isoforms in the same tissue.

Original languageEnglish
Pages (from-to)97-105
Number of pages9
JournalJournal of Clinical Investigation
Volume108
Issue number1
DOIs
StatePublished - Jul 24 2001

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Thyroid Hormone Receptors
Thermogenesis
Thyroid Hormones
Protein Isoforms
Brown Adipose Tissue
Adrenergic Agents
Brown Adipocytes
Sympathetic Nervous System
Body Temperature
GC 1 compound
Mammals
Norepinephrine
Thyroid Gland
Pharmacology
Ligands
Messenger RNA
Temperature
Uncoupling Protein 1
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ribeiro, M. O., Carvalho, S. D., Schultz, J. J., Chiellini, G., Scanlan, T. S., Bianco, A. C., & Brent, G. A. (2001). Thyroid hormone-sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform-specific. Journal of Clinical Investigation, 108(1), 97-105. https://doi.org/10.1172/JCI200112584

Thyroid hormone-sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform-specific. / Ribeiro, M. O.; Carvalho, S. D.; Schultz, J. J.; Chiellini, G.; Scanlan, T. S.; Bianco, A. C.; Brent, G. A.

In: Journal of Clinical Investigation, Vol. 108, No. 1, 24.07.2001, p. 97-105.

Research output: Contribution to journalArticle

Ribeiro, MO, Carvalho, SD, Schultz, JJ, Chiellini, G, Scanlan, TS, Bianco, AC & Brent, GA 2001, 'Thyroid hormone-sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform-specific', Journal of Clinical Investigation, vol. 108, no. 1, pp. 97-105. https://doi.org/10.1172/JCI200112584
Ribeiro, M. O. ; Carvalho, S. D. ; Schultz, J. J. ; Chiellini, G. ; Scanlan, T. S. ; Bianco, A. C. ; Brent, G. A. / Thyroid hormone-sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform-specific. In: Journal of Clinical Investigation. 2001 ; Vol. 108, No. 1. pp. 97-105.
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