Dominant role of thyrotropin-releasing hormone in the hypothalamic- pituitary-thyroid axis

Amisra A. Nikrodhanond, Tania M. Ortiga-Carvalho, Nobuyuki Shibusawa, Koshi Hashimoto, Hui Liao Xiao, Samuel Refetoff, Masanobu Yamada, Masatomo Mori, Fredric E. Wondisford

Research output: Contribution to journalArticlepeer-review


Hypothalamic thyrotropin-releasing hormone (TRH) stimulates thyroid-stimulating hormone (TSH) secretion from the anterior pituitary. TSH then initiates thyroid hormone (TH) synthesis and release from the thyroid gland. Although opposing TRH and TH inputs regulate the hypothalamic-pituitary- thyroid axis, TH negative feedback is thought to be the primary regulator. This hypothesis, however, has yet to be proven in vivo. To elucidate the relative importance of TRH and TH in regulating the hypothalamic-pituitary-thyroid axis, we have generated mice that lack either TRH, the β isoforms of TH receptors (TRβ KO), or both (double KO). TRβ knock-out (KO) mice have significantly higher TH and TSH levels compared with wild-type mice, in contrast to double KO mice, which have reduced TH and TSH levels. Unexpectedly, hypothyroid double KO mice also failed to mount a significant rise in serum TSH levels, and pituitary TSH immunostaining was markedly reduced compared with all other hypothyroid mouse genotypes. This impaired TSH response, however, was not due to a reduced number of pituitary thyrotrophs because thyrotroph cell number, as assessed by counting TSH immunopositive cells, was restored after chronic TRH treatment. Thus, TRH is absolutely required for both TSH and TH synthesis but is not necessary for thyrotroph cell development.

Original languageEnglish (US)
Pages (from-to)5000-5007
Number of pages8
JournalJournal of Biological Chemistry
Issue number8
StatePublished - Feb 24 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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