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

Biochemical and Biophysical Research Communications
Y HayashiS Refetoff

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) beta (G345R) was targeted to the pituitary thyrotrophs by placing it downstream of the mouse thyrotropin beta promoter. This construct exhibited an antagonistic effect on the thyroid hormone-dependent transactivation, mediated through the wild-type TRbeta1, only when cotransfected 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.

References

Jan 1, 1994·Thyroid : Official Journal of the American Thyroid Association·S Refetoff
Jan 1, 1994·Thyroid : Official Journal of the American Thyroid Association·P Beck-Peccoz, V K Chatterjee

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Citations

Dec 17, 2002·Thyroid : Official Journal of the American Thyroid Association·Ilan ShimonDavid Olchovsky
Jan 23, 1999·The Journal of Clinical Investigation·E D AbelF E Wondisford
Jun 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Paul Webb
Nov 9, 2000·Proceedings of the National Academy of Sciences of the United States of America·M KaneshigeS Cheng
Apr 25, 2000·Thyroid : Official Journal of the American Thyroid Association·D A FisherR B Wilcox
Dec 14, 1999·Thyroid : Official Journal of the American Thyroid Association·X G ZhuS Y Cheng
Feb 11, 2016·Endocrine Reviews·J H Duncan Bassett, Graham R Williams
Jun 28, 2001·Physiological Reviews·P M Yen

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