Nongenomic Actions of Thyroid Hormones: Focus on Membrane Transport Systems

Author(s): R. N. Farias, A. M. Fiore, J. Z. Pedersen, S. Incerpi.

Journal Name: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued)

Volume 6 , Issue 3 , 2006

Abstract:

Extranuclear or nongenomic effects of thyroid hormones are unaffected by inhibitors of protein synthesis, and their rapid time course cannot be explained by interaction of the hormone molecule with nuclear receptors. Their origin has been localized at the plasma membrane, but also at organelles such as the endoplasmatic reticulum and mitochondria. Thyroid hormone has been reported to activate, by both genomic and non genomic mechanisms, the Ca2+-ATPase that stores calcium from the cytosol in the sarcoplasmic reticulum; the decrease in intracellular Ca2+ leads to muscle relaxation. Considering the important effects on the cardiovascular system, T3 can actually be envisaged as a potent inotropic drug. T3 is also a major regulator of the plasma membrane Na+/K+-ATPase activity; T3 and its analog 3,5-diiodothyronine rapidly inhibits Na+/K+-ATPase in chick embryo hepatocytes, whereas the activity is up-regulated in alveolar epithelial cells. Also the ubiquitous plasma membrane Na+/H+ exchanger, that regulates cell volume and pH by exchanging extracellular Na+ with cytoplasmic H+ according to the concentration gradient, is activated by T3 via both genomic and nongenomic mechanisms. A growing number of natural and synthetic thyroid hormone analogs are available to study the physiological importance of extranuclear effects; this may lead to compounds that selectively target either genomic or nongenomic receptors. Such drugs may make it possible to activate separately only a part of the complex effects normally induced by thyroid hormones, this could be of clinical relevance for the cardiovascular system, bone tissue and the Central Nervous System.

Keywords: Thyroid hormone, ion transport, Ca2+-transport, Na+/H+ exchanger, Na+/K+-ATPase, amino acid transport

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Article Details

VOLUME: 6
ISSUE: 3
Year: 2006
Page: [241 - 254]
Pages: 14
DOI: 10.2174/187152206777435609
Price: $58

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