Critical role for thyroid hormone receptor β2 in the regulation of paraventricular thyrotropin-releasing hormone neurons

E. Dale Abel, R. S. Ahima, M. E. Boers, J. K. Elmquist, F. E. Wondisford

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Abstract

Thyroid hormone thyroxine (T4) and tri-iodothyronine (T3) production is regulated by feedback inhibition of thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) synthesis in the pituitary and hypothalamus when T3 binds to thyroid hormone receptors (TRs) interacting with the promoters of the genes for the TSH subunit and TRH. All of the TR isoforms likely participate in the negative regulation of TSH production in vivo, but the identity of the specific TR isoforms that negatively regulate TRH production are less clear. To clarify the role of the TR-β2 isoform in the regulation of TRH gene expression in the hypothalamic paraventricular nucleus, we examined preprothyrotropin-releasing hormone (prepro-TRH) expression in mice lacking the TR-β2 isoform under basal conditions, after the induction of hypothyroidism with propylthiouracil, and in response to T3 administration. Prepro-TRH expression was increased in hypothyroid wild-type mice and markedly suppressed after T3 administration. In contrast, basal TRH expression was increased in TR-β2-null mice to levels seen in hypothyroid wild-type mice and did not change significantly in response to induction of hypothyroidism or T3 treatment. However, the suppression of TRH mRNA expression in response to leptin reduction during fasting was preserved in TR-β2-null mice. Thus TR-β2 is the key TR isoform responsible for T3-mediated negative-feedback regulation by hypophysiotropic TRH neurons.

Original languageEnglish (US)
Pages (from-to)1017-1023
Number of pages7
JournalJournal of Clinical Investigation
Volume107
Issue number8
StatePublished - 2001

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Thyroid Hormone Receptors
Thyrotropin-Releasing Hormone
Neurons
Protein Isoforms
Hypothyroidism
Thyroxine
Pituitary Hormone-Releasing Hormones
Propylthiouracil
Paraventricular Hypothalamic Nucleus
Thyrotropin
Leptin
Hypothalamus
Fasting
Gene Expression
Messenger RNA

ASJC Scopus subject areas

  • Medicine(all)

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Critical role for thyroid hormone receptor β2 in the regulation of paraventricular thyrotropin-releasing hormone neurons. / Dale Abel, E.; Ahima, R. S.; Boers, M. E.; Elmquist, J. K.; Wondisford, F. E.

In: Journal of Clinical Investigation, Vol. 107, No. 8, 2001, p. 1017-1023.

Research output: Contribution to journalArticle

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