Nongenomic actions of L-thyroxine and 3, ,3'-triiodo-L-thyronine. Focus on 'L-Thyroxine vs. 3, 5,3'-triiodo-L-thyronine and cell proliferation: activation of mitogen-activated protein kinase and phosphatidyrinositol 3-kinase'

摘要

the molecular mechanisms of the numerous cellular actions of thyroid hormone have been widely studied. The classical mechanism of thyroid hormone action occurs by uptake of L-thyroxine (T4) or 3, 5,3' triiodo-L-thyronine (T_3) into cells, transport into the cell nucleus, binding with a thyroid receptor (TR), recruitment of coactivators, and regulation of gene transcription via thyroid response elements (TRE). T_3 is more potent in these actions than T_4. These genomic actions require access of the hormone to the cell interior, translocation to the nucleus, alteration of the rate of gene transcription, and translation of the specific gene product; thus, the overall response generally requires several hours to become manifest. Over the past decade, many actions of thyroid hormone have been described that do not involve initial nuclear action of thyroid receptors and/or gene transcription; therefore they are considered "nongenomic" (6). Davis and colleagues (6, 7) have described both TR-dependent and TR-independent novel nongenomic actions that involve cell surface receptors and signal transduction pathways. Some actions that begin nongenomically at the cell surface may ultimately become nuclear and cellular events. One example is the phosphor-ylation of the TRβ by T_4 that results in derepression of the transcriptional activity of SMRT (silencing mediator of retinoid and thyroid hormone receptor) by dissociation of TR and SMRT (7). Another example is that thyroid hormone promotes cell proliferation via nongenomic actions in the chick chorioallantoic membrane model (4) and in glioma cells (5).