THs & Growth Factors

What is it about?

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. 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 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 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, 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 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. Keywords: Early pregnancy, extravillous trophoblast, integrin, matrix Gla protein, myokine, nerve cell, nerve growth factor, nongenomic.

Featured Image

Why is it important?

Thyroid hormone involvement in a variety of metabolic and developmental processes is now widely acknowledged, and their interaction with growth factors represents an additional mechanism that may explain such processes. Understanding the role of thyroid hormones in this crosstalk may facilitate the development of new tools for therapeutic intervention, and in this context the nanotetrac formulation appears to be very promising. In this review we have focused on new developments in the field for reasons of space, but further examples can be found in recent reviews on thyroid hormone nongenomic effects concerning membrane transport systems [143], immune activities [144, 145], skeletal muscle [146], molecular aspects [147], and the possible clinical applications [148, 149]. Some of these effects are summarized in Fig. (2).

Perspectives