Abstract
Hönes et al. have recently shown that in vivo interference with the apparatus of the nuclear receptor-mediated, gene-driven mechanism of triiodothyronine (T3) actions fails to eliminate all actions of T3. However, the investigators conducting that study provided little information regarding the mechanisms that might be responsible for conferring those implied gene-independent effects. Dratman has long ago suggested a system wherein such gene-free mechanisms might operate. Therefore, since news of that discovery was originally published in 1974, it seems appropriate to describe the progress made since then. We propose that thyroxine and triiodothyronine have many different structural properties that may confer a series of different capabilities on their functions. These conform with our proposal that a series of catecholamine analogs and their conversion to iodothyronamines, allows them to perform many of the functions that previously were attributed to nuclear receptors regulating gene expression. The actions of deiodinases and the differential distribution of iodine substituents are among the critical factors that allow catecholamine analogs to change their effects into ones that either activate their targets or block them. They do this by using two different deiodinases to vary the position of an iodide ion on the diphenylether backbones of thyroxine metabolites. A panoply of these structural features imparts major unique functional properties on the behavior of vertebrates in general and possibly on Homo sapiens in particular.
Highlights
In the early 1900s, Kendall [1] and Harington [2], each working independently in his own laboratory, contributed to the discovery of thyroxine as the principle agent of thyroid hormone action
Hönes et al have recently shown that in vivo interference with the apparatus of the nuclear receptor-mediated, gene-driven mechanism of triiodothyronine (T3) actions fails to eliminate all actions of T3
We propose that thyroxine and triiodothyronine have many different structural properties that may confer a series of different capabilities on their functions
Summary
In the early 1900s, Kendall [1] and Harington [2], each working independently in his own laboratory, contributed to the discovery of thyroxine as the principle agent of thyroid hormone action. Their research soon led each of them to present various versions of the proposed structure of that ubiquitous compound: thyroxine. Neither investigator mentioned the amino acid character of their proposed thyroxine’s chemistry (see Figure 1), it could have been deduced from each of the many chemical formulae of putative thyroxine molecules that they proposed and struggled to justify as the active agent of thyroid follicle function. He proposed a version of thyroxine’s structure which, though later somewhat modified, became widely accepted [3]. The dogma persisted because, unlike thyroxine’s effect on almost all other rodent tissues, brain tissue failed to increase its level of oxygen consumption after administration of thyroxine [4,5]. As a result of those observations, thyroxine’s action in the brain was, for a considerable period of years, ignored by investigators seeking to understand the mechanism of thyroxine’s action in vertebrate organisms, especially in rodents such as rats and mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
