Open AccessGeneralized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor beta.
Author(s) -
Akihiro Sakurai,
Kyoko Takeda,
Kenneth B. Ain,
P. Ceccarelli,
Asami Nakai,
Susumu Seino,
Graeme I. Bell,
Samuel Refetoff,
Leslie J. DeGroot
Publication year - 1989
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.86.22.8977
Subject(s) - thyroid hormone receptor beta , thyroid hormone receptor , thyroid , thyroid hormone receptor alpha , endocrinology , medicine , hormone , triiodothyronine , nuclear receptor , hormone receptor , growth hormone releasing hormone receptor , biology , genetics , gene , cancer , transcription factor , breast cancer
The syndrome of generalized resistance to thyroid hormone is characterized by elevated circulating levels of thyroid hormone in the presence of an overall eumetabolic state and failure to respond normally to triiodothyronine. We have evaluated a family with inherited generalized resistance to thyroid hormone for abnormalities in the thyroid hormone nuclear receptors. A single guanine----cytosine replacement in the codon for amino acid 340 resulted in a glycine----arginine substitution in the hormone-binding domain of one of two alleles of the patient's thyroid hormone nuclear receptor beta gene. In vitro translation products of this mutant human thyroid hormone nuclear receptor beta gene did not bind triiodothyronine. Thus, generalized resistance to thyroid hormone can result from expression of an abnormal thyroid hormone nuclear receptor molecule.