Paradigms of Dynamic Control of Thyroid Hormone Signaling.

Paradigms of Dynamic Control of Thyroid Hormone Signaling. Endocr Rev. 2019 Apr 29;: Authors: Bianco AC, Dumitrescu A, Gereben B, Ribeiro MO, Fonseca TL, Fernandes GW, Bocco BMLC Abstract Thyroid hormone (TH) molecules enter cells via membrane transporters and, depending on the cell type, can be activated, that is thyroxine (T4) to 3,5,3'-tri-iodothyronine (T3) conversion, or inactivated - T3 to 3,3'-diiodo-L-thyronine (T2) or T4 to reverse tri-iodothyronine (rT3) conversion. These reactions are catalyzed by the deiodinases. The biologically active hormone, T3, eventually binds to intracellular TH receptors (TR), TRα and TRβ, and initiate TH signaling, i.e. regulation of target genes and other metabolic pathways. At least three families of transmembrane transporters, MCT, OATP and LAT, facilitate the entry of TH into cells, which follow the gradient of free hormone between the extracellular fluid and the cytoplasm. Inactivation or marked downregulation of TH transporters can dampen TH signaling. At the same time, dynamic modifications in the expression or activity of TRs and transcriptional co-regulators can affect positively or negatively the intensity of TH signaling. However, the deiodinases are the element that provides greatest amplitude in dynamic control of TH signaling. Cells that express the activating deiodinase DIO2 can rapidly enhance TH signaling due to intracellular build-up of T3. In contrast, TH signaling is dampene...
Source: Endocrine Reviews - Category: Endocrinology Tags: Endocr Rev Source Type: research