Thyroid Hormones. From Molecular Signaling to Human Disease: An Update

This Thematic Issue presents reviews of recent studies on effects of thyroid hormones and certain metabolites that are linked to human diseases, providing a general update of the topic. I have been the guest editor for thematic issues of IEMAMC for three times, in 2006, 2011 and 2015, and over these 10 years my knowledge of the nongenomic effects of thyroid hormone has improved considerably. First issue was dedicated to the nongenomic effects of various hormones endowed with classical nuclear receptors, and included a chronology of the earliest reported nongenomic effects of thyroid hormones. Second issue was centered on thyroid hormone nongenomic mechanisms in skeletal muscle and nerve cells, mainly, but not exclusively, dealing with effects mediated by integrin alphaVbeta3. In the current issue, the coverage of thyroid hormone actions is wider, including also nuclear classical effects, the cognitive processes and effects of some hormone metabolites that are particularly interesting from pharmacological point of view. Why? When a new surprising discovery is published, such as the seminal paper by Bergh et al., in 2005, showing that the integrin alphaVbeta3 was the long-searched plasma membrane receptor for thyroid hormones, it can of course dominate the scenery for years, and other researchers in this field will use this new piece of information in their studies to understand the physio-pathological effects of thyroid hormones. The Bergh et al. paper showed that binding by thyroxine to the integrin alphaVbeta3 gives rise to a downstream signaling that causes MAPK activation and tumor cell proliferation. This has so to say been the ‘Big Bang’ of nongenomic effects of thyroid hormones. After ten years of the integrin story, we can now observe how many things have changed in our knowledge about the role of thyroid hormones in animal physiology. However, actually the integrin story began before alphaVbeta3 was recognized as a plasma membrane thyroid hormone receptor. The group of Davis and Davis showed, in 2004, that various effects of thyroid hormone on the actions of epidermal growth factor and transforming growth factor-alpha were mediated by cAMP-dependent protein kinase II. The crosstalk between thyroid hormones and growth factors reported in that paper would eventually lead to the integrin; alphaVbeta3 was ‘in nuce’ although it was not clear at that time. Now, this interaction of thyroid hormones with growth factors is coming of age and may lead us far, to different and still unknown aspects of physiology and pathology, as it can be observed from some of the contributions in this issue.