Selective pituitary resistance to thyroid hormone produced by expression of a mutant thyroid hormone receptor β gene in the pituitary gland of transgenic mice

Yoshitaka Hayashi, Jun Xie, Roy E. Weiss, Joachim Pohlenz, Samuel Refetoff

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Resistance to thyroid hormone (RTH) has been subdivided into generalized resistance (GRTH) and pituitary resistance (PRTH) based on the clinical impression of absence or presence of thyrotoxicosis. However, due to lack of objective clinical and genetic criteria, the existence of PRTH as a distinct entity became controversial. To determine what the phenotype would be if RTH was confined to the pituitary, a transgenic mouse was developed in which expression of the mutant thyroid hormone receptor (TR) β (G345R) was targeted to the pituitary thyrotrophs by placing it downstream of the mouse thyrotropin β promoter. This construct exhibited an antagonistic effect on the thyroid hormone-dependent transactivation, mediated through the wild-type TRβ1, only when co-transfected with the thyrotroph embryonic factor in a heterologous cell line. As expected the transgene was transcribed predominantly in the pituitary gland but not in liver. These mice showed a significant, though modest, increase in serum T4 concentration. A decrease in the serum cholesterol was observed in keeping with the selective tissue hyposensitivity to thyroid hormone.

Original languageEnglish (US)
Pages (from-to)204-210
Number of pages7
JournalBiochemical and biophysical research communications
Volume245
Issue number1
DOIs
StatePublished - Apr 7 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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