PMID: 9430820Feb 7, 1998Paper

Regulation of the human TRH (hTRH) gene by human thyroid hormone receptor beta 1 (hTR beta 1) mutants

Endocrine Research
Q L LiJ F Wilber

Abstract

TRH is negatively regulated by T3 both in the hypothalamic paraventricular nucleus and transient transfection models. Mutations in hTR beta 1 genes are associated with the syndrome of generalized resistance to thyroid hormone. To investigate potential effects of mutant TRs on T3 regulation of the hTRH gene, transient gene expression assays were performed in human neuroblastoma (HTB-11) cells with an hTRH promoter-luciferase construct, wild type (WT) hTR beta 1, and three qualitatively distinct hTR beta 1 mutant forms (ED, OK and PV). In the presence of T3 (10(-9) M), liganded WT-hTR beta 1 inhibited hTRH promoter activity significantly (40%). Cotransfection of each of the two mutants (ED and OK) achieved similar levels of inhibition only at 10 to 100 fold increased T3 concentrations. Of interest, a 10x excess of mutant ED or OK could also exert dominant negative effects upon WT hTR beta 1-T3 mediated inhibitory actions on the hTRH promoter. In contrast, mutant TR-PV exerted neither inhibitory nor dominant negative effects at even higher concentrations of T3. Moreover, all three unliganded mutant forms stimulated TRH promoter activity significantly in the absence of T3, despite their different mutations in the ligand-binding dom...Continue Reading

References

Jan 1, 1992·Hormone Research·C JaffiolJ Torresani
Jan 1, 1992·Hormone Research·P Beck-PeccozG Faglia
Oct 1, 1993·The Journal of Pediatrics·R E WeissS Refetoff
Oct 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A BaniahmadB W O'Malley

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Citations

Dec 9, 2004·American Journal of Physiology. Endocrinology and Metabolism·Xiaoxiong ShenTheodore C Friedman
Dec 20, 2000·American Journal of Physiology. Endocrinology and Metabolism·Q L LiT C Friedman
Feb 1, 2013·Journal of Thyroid Research·Johannes W DietrichElisavet H Fotiadou
Aug 13, 2021·Thyroid : Official Journal of the American Thyroid Association·Peter LaufferA S Paul van Trotsenburg

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