Noncanonical Action of Thyroid Hormone Receptors α and β
Exp Clin Endocrinol Diabetes DOI: 10.1055/a-1088-1187Thyroid hormone (TH) is essential for the regulation of many physiological
processes, especially growth, organ development, energy metabolism and
cardiovascular effects. TH acts via the TH receptors (TR) α and
β. By binding to thyroid hormone responsive elements (TREs) on the DNA,
TRs regulate expression of TH target genes. Thus, TRs are mainly characterized
as ligand dependent transcription factors and regulation of gene expression and
protein synthesis is considered the canonical mode of TH/TR action. The
demonstration that the ligand-bound TRs α and β also mediate
activation of the phosphatidylinositol-3-kinase (PI3K) pathway established
noncanonical TH/TR action as an additional mode of TH signaling.
Recently, TR mutant mouse models allowed to determine the underlying mode of
TH/TR action, either canonical or noncanonical TH/TR signaling,
for several physiological TH effects in vivo: Regulation of the
hypothalamic-pituitary-thyroid axis requires DNA-binding of TRβ, whereas
hepatic triglyceride content appears to be regulated by noncanonical TRβ
signaling. TRα mediated effects in bone development are dependent on
DNA-binding, whereas several cardiovascular TRα effects are rapid and
independent from DNA-binding. Therefore, noncanonical TH/TR actio...
Source: Experimental and Clinical Endocrinology and Diabetes - Category: Endocrinology Authors: H önes, G. Sebastian Geist, Daniela Moeller, Lars C. Tags: Article Source Type: research
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