Title:Thyroid Hormones Crosstalk with Growth Factors: Old Facts and New Hypotheses
Volume: 15
Issue: 1
Author(s): Elena Candelotti, Paolo De Vito, Ragab G. Ahmed, Paolo Luly, Paul J. Davis, Jens Z. Pedersen, Hung-Yun Lin and Sandra Incerpi
Affiliation:
Keywords:
Early pregnancy, extravillous trophoblast, integrin , matrix Gla protein, myokine, nerve cell, nerve growth
factor, nongenomic.
Abstract: Nongenomic effects of thyroid hormones typically start at the cell surface and do not primarily
involve the classical nuclear receptors, but rather a plasma membrane receptor site identified
about ten years ago on the integrin αvβ. Transduction of the thyroid hormone signal from this integrin
receptor involves activation of the MAPK pathway and may lead to events such as angiogenesis or tumor cell proliferation.
This review focuses on the interaction of thyroid hormones with growth factors, in fact the integrin αvβ3 has
been reported to a be a co-receptor for several growth factors such as EGF, IGF-1 and the FGF family, but also for small
molecules like resveratrol. Binding of the ligand to integrin αvβ3 is inhibited by tetrac, a metabolite of L-thyroxine, and
by its nanoparticulate formulation nanotetrac. Recent microarray studies on tumor cells have shown that tetrac has antiinflammatory
effects that are mediated by integrin αvβ3, and tetrac can downregulate the expression of several interleukin
genes. Crosstalk between thyroid hormones and vascular growth factors is important for cell migration, vascular calcification
and the angiogenic process. Thyroid hormones also show pleiotropic effects on osteoblast function and differentiation,
as well as in early pregnancy. The importance of thyroid hormone interaction with neurotrophins and interleukins has
also been examined. With integrin αvβ3 firmly established as the plasma membrane receptor future studies will focus on
the crosstalk between thyroid hormones and growth factors in order to verify the efficiency of new pharmacological tools,
such as nanotetrac.