Somatic mutation of TRbeta can cause a defect in negative regulation of TSH in a TSH-secreting pituitary tumor.

Published

Journal Article

In patients with TSH-secreting tumors (TSHomas), serum TSH is poorly suppressed by thyroid hormone. The mechanism for this defect in negative regulation of TSH secretion is not known. To investigate the possibility of a somatic mutation of TR causing this defect, we performed mutational analysis of TRbeta by RT-PCR using RNA obtained from five surgically resected TSHomas. In one TSHoma, we identified a somatic mutation in the ligand-binding domain of TRbeta that caused a His to Tyr substitution at codon 435 of TRbeta1 corresponding to codon 450 of TRbeta2. Interestingly, this mutation occurred in the same codon as two mutations (TRbetaH435L and H435Q) previously identified in patients with the syndrome of resistance to thyroid hormone. This mutant TRbeta had impaired T3 binding and T3-mediated negative regulation. It also blocked the negative regulation by wild-type TRbeta2 on glycoprotein hormone alpha-subunit and TSHbeta reporter genes in cotransfection studies. Our results demonstrate that somatic mutation of TRbeta occurred in a TSHoma and was probably responsible for the defect in negative regulation of TSH by thyroid hormone in the tumor.

Full Text

Duke Authors

Cited Authors

  • Ando, S; Sarlis, NJ; Oldfield, EH; Yen, PM

Published Date

  • November 2001

Published In

Volume / Issue

  • 86 / 11

Start / End Page

  • 5572 - 5576

PubMed ID

  • 11701737

Pubmed Central ID

  • 11701737

International Standard Serial Number (ISSN)

  • 0021-972X

Digital Object Identifier (DOI)

  • 10.1210/jcem.86.11.7984

Language

  • eng

Conference Location

  • United States