Nongenomic Actions of Thyroid Hormones: Every why has a Wherefore

Author(s): Ariane Zamoner, Regina Pessoa-Pureur.

Journal Name: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization)

Volume 11 , Issue 3 , 2011

Abstract:

Thyroid hormones 3,5,3-triiodo-L-thyronine (T3) and thyroxine (T4) are important metabolic and physiological regulators of many tissues within the body during development and in adulthood. These effects have largely been attributed to the modulation of thyroid hormone receptor-dependent gene transcription. However, nongenomic actions of thyroid hormones are emerging in a number of cell types. These actions require a plasma membrane receptor or nuclear receptors located in cytoplasm. Several studies propose that this actions are initiated by activation of N-methyl-D-aspartate (NMDA)-, γ-amino butyric acid (GABA)- or G protein-coupled receptors. Recently, the receptor integrin αVβ3 at the Arg-Gly-Asp recognition site has been described to mediate actions of T3 and T4. The hormone-evoked signal is transduced downstream Ca2+ mobilization or monomeric GTPase activation through different kinase pathways, including protein kinase A, protein kinase C and the mitogen-activated protein kinases (MAPKs), into complex cellular/nuclear events. These findings support the contention that thyroid hormones have a variety of nongenomic pathways regulating many important aspects of cell physiology. Among the most relevant nongenomic effects of thyroid hormones is the regulation of the cytoskeleton. This review focuses on the current knowledge and important results on the mechanisms of nongenomic thyroid action with special emphasis on the cytoskeletal proteins and their differential regulation by kinases and Ca2+- mediated mechanisms in developmental rat brain. The roles of Ca2+ mobilization and subsequent cytoskeletal protein phosphorylation are crucial biological markers that have been shown to be the essence of brain development and preservation of cognitive functions.

Keywords: Brain, calcium, cytoskeleton, nongenomic mechanisms, protein phosphorylation, thyroid hormones, intermediate filaments, microfilaments, GABAergic signaling, nongenomic mechanism, Rho-GTPases, protein kinases signaling

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Article Details

VOLUME: 11
ISSUE: 3
Year: 2011
Page: [165 - 178]
Pages: 14
DOI: 10.2174/187152211796642765
Price: $58

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