+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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 245(1): 204-210



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 009392933

Download citation: RISBibTeXText

PMID: 9535809

DOI: 10.1006/bbrc.1998.8396


Related references

An intronic SNP in the thyroid hormone receptor beta gene is associated with pituitary cell-specific over-expression of a mutant thyroid hormone receptor beta-2 R338W in the index case of pituitary-selective resistance to thyroid hormone. 2011

An intronic SNP in the thyroid hormone receptor β gene is associated with pituitary cell-specific over-expression of a mutant thyroid hormone receptor β2 (R338W) in the index case of pituitary-selective resistance to thyroid hormone. Journal of Translational Medicine 9: 144, 2011

Selective chemical rescue of a thyroid-hormone-receptor mutant, TRbeta(H435Y), identified in pituitary carcinoma and resistance to thyroid hormone. Angewandte Chemie 47(38): 7280-7283, 2008

Dominant inhibition of thyroid hormone action selectively in the pituitary of thyroid hormone receptor-beta null mice abolishes the regulation of thyrotropin by thyroid hormone. Molecular Endocrinology 17(9): 1767-1776, 2003

Expression of the mutant thyroid hormone receptor PV in the pituitary of transgenic mice leads to weight reduction. Thyroid 9(11): 1137-1145, 1999

A Novel Thyroid Hormone Receptor Beta Gene Mutation (G251V) in a Thai Patient with Resistance to Thyroid Hormone Coexisting with Pituitary Incidentaloma. Thyroid 26(12): 1804-1806, 2016

Genetic analysis of 29 kindreds with generalized and pituitary resistance to thyroid hormone. Identification of thirteen novel mutations in the thyroid hormone receptor beta gene. Journal of Clinical Investigation 94(2): 506-515, 1994

T3 and dna binding properties of a mutant thyroid hormone receptor associated with pituitary resistance to thyroid hormone. Clinical Research 40(1): 77A, 1992

Mutagenesis of a novel thyroid hormone receptor domain responsible for selective pituitary resistance to thyroid hormone. Journal of Investigative Medicine 43(Suppl. 2): 224A, 1995

A transgenic model of resistance to thyroid hormone Correlation of mutant thyroid hormone beta-1 receptor levels with the phenotype of fat loss and hyperactivity. Journal of Investigative Medicine 43(Suppl. 2): 223A, 1995

Pituitary resistance to thyroid hormone caused by a novel mutation (H435A) in the thyroid hormone receptor beta: A case report. Medicine 97(21): E10544, 2018

Identification of a novel mutation in the gene encoding the beta-triiodothyronine receptor in a patient with apparent selective pituitary resistance to thyroid hormone. Clinical Endocrinology 38(3): 227-234, 1993

Pituitary thyroid hormone resistance caused by a novel mutation in the beta isoform of the thyroid hormone receptor. Clinical Research 42(2): 208A, 1994

A novel thyroid hormone receptor-beta mutation that fails to bind nuclear receptor corepressor in a patient as an apparent cause of severe, predominantly pituitary resistance to thyroid hormone. Journal of Clinical Endocrinology and Metabolism 91(5): 1887-1895, 2006

A mouse model of resistance to thyroid hormone produced by somatic gene transfer of a mutant thyroid hormone receptor. Molecular Endocrinology 10(1): 100-106, 1996