Title:Nongenomic Actions of Thyroid Hormones: From Basic Research to Clinical Applications. An Update
Volume: 13
Issue: 1
Author(s): R. G. Ahmed, Paul J. Davis, Faith B. Davis, Paolo De Vito, Ricardo N. Farias, Paolo Luly, Jens Z. Pedersen and Sandra Incerpi
Affiliation:
Keywords:
Cardiovascular system, immune system, integrin, ion transport, MAPK, mTOR, Na+/K+-ATPase, nerve cells.
Abstract: Extranuclear or nongenomic actions of thyroid hormones are unaffected by the inhibitors of protein synthesis,
their site of action has been localized at the plasma membrane but also in the cytoplasm and organelles such as the mitochondria.
This review takes into account recent major advances in nongenomic effects of thyroid hormones in nervous
system, immune system and cardiovascular tissue, with a particular focus on the plasma membrane receptor integrin αvβ3.
In nerve cells nongenomic effects of thyroid hormones point mainly to a direct modulation of several channels/receptors
for the major neurotransmitters, even though more complex pathways have also been demonstrated. Certain neuroprotective
actions have recently been described for thyronamines, and this may be relevant to Alzheimer’s disease and multiple
sclerosis. The immune system is also modulated nongenomically by thyroid hormones, through potentiation of the effects
of cytokines such as IFN-γ or lipopolysaccharide, or through activators of STAT protein leading to activation of the
mammalian target of rapamycin (mTOR) pathway, a highly conserved kinase downstream target of nongenomic actions
of thyroid hormone. The mTOR system is also involved in the cardioprotection mechanisms, where thyroid hormone signaling
through the receptor integrin αvβ3 may play an important role that needs to be further studied. The identification of
integrin αvβ3 as a plasma membrane receptor for thyroid hormones has provided a new perspective on the role of these
hormones in cellular defense. Analogs of thyroid hormones, inhibitors and agonists at the integrin receptor for the hormone
and mTOR inhibitors are evaluated as areas of emphasis for therapeutic research.
