Iodine and related biological iodine-carrying hormones are phylogenetically very old, at least according to Wikipedia. Humans use iodine as a metabolic indicator, as do axolotls and apparently most multicellular life.

So why? Growth hormones, sex hormones, et cetera don't require strange heavy elements not used for anything else. It's not a requirement of transcription factors that they contain iodine.

All I've got for hints is that selenium forms an essential part of deiodinases, as well as forming an essential part of thioredoxin reductase. Thioredoxin is a component used to reduce things around the cell, like thiols and RNA bits and so on and so forth, which I could see being worth the evolutionary cost of running down some selenium.

What's the point of iodine? People have iodine deficiency 'all the time' (it's common enough to be named). Is that a product of agriculture somehow? Are there any advantages to using iodine for metabolic hormones? If there are, what are they?

  • $\begingroup$ It's an interesting question, though I'm not sure it's answerable. This may be vaguely insightful (I have only read the abstract): ncbi.nlm.nih.gov/m/pubmed/7381861/?i=2&from=/684433/related $\endgroup$
    – canadianer
    Feb 10 '15 at 7:32
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    $\begingroup$ It may not be correct to say that iodine is a requirement of metabolic hormones; I imagine that the evolution of another system is entirely feasible. Perhaps it's a remnant of some species that had access to excess iodine, which provided a mechanism to easily create a different tyrosine-derived hormone to fill some niche. $\endgroup$
    – canadianer
    Feb 10 '15 at 7:38
  • $\begingroup$ There are two possiblities. Either iodine is useful in its own right in some way, or lack of iodine is not a concern. I don't know enough about iodine metabolism, excretion etc to know if iodine deficiency is even a thing in nonhuman animals. If it's not a thing, what is it about humans that makes them susceptible? Is it agriculture or something? $\endgroup$
    – Resonating
    Feb 10 '15 at 7:56
  • $\begingroup$ Thyroid hormone functions generally require they bind to specific receptor proteins, and some of these receptors undergo specific conformational changes that alter activation/repression dynamics in the nucleus. Iodines might assist in that respect, esp. given Canadianer's article. vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/… $\endgroup$
    – CKM
    Feb 10 '15 at 17:24
  • $\begingroup$ The specific receptor proteins are tuned to recognize thyroid hormones containing iodine, yes. Most transcription factors don't require a rare trace element, and there's a distinct fitness cost to it(at least in modern humans). So what's the payoff? Why do most multicellular organisms use such a specific and rare element? HGH, leptin, ghrelin, etcetera all don't require iodine. Other evolutionary solutions are possible $\endgroup$
    – Resonating
    Feb 10 '15 at 21:22

Classical thyroid hormones implement a very flexible signaling mechanism. Basically, they comprise two aromatic rings that are connected via an oxygen atom. Optionally, they may contain organic side chains and inorganic iodine atoms.

In the case of iodothyronines, which are represented e.g. by the well-known thyroid hormones T4, T3 and 3,5-T2, the side chain contains an amino group and a carboxylate group. Therefore, iodothyronines are amino acids. Up to four different hydrogen atoms (two at every ring) may be replaced by iodine atoms, and the resulting pattern of iodination determines their biological activity. Generally, iodination of the inner ring and deiodination of the outer ring results in high biological activity (e.g. in T3 and 3,5-T2), whereas iodination of the outer ring and deiodination of the inner ring delivers a receptor-blocking thyroid hormone (e.g. reverse-T3). There are three deiodinases encoded by the DIO1, DIO2 and DIO3 genes that catalyze the "step-up" and "step-down" reactions to active or inactive thyroid hormones, respectively. Multiple molecular processes are able to differentially upregulate and downregulate tissue deiodinases. Therefore, thyroid hormones are subject to both global and local control.

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Removal of the amino group results in iodothyroacetates. Their biological effects are similar to those of iodothyronines, but in addition to nuclear receptors they also have a strong effect on membrane-bound receptors, which are only weakly activated by iodothyronines.

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Thyronamines lack the carboxylate group. Their biological effect is different to that of iodothyronines and iodothyroacetates. By activating the membrane-bound TAAR1 receptor they have an effect that is in most respects antagonistic to that of classical thyroid hormones. Thyronamines seem to be most active in deiodinated state.

enter image description here

Summarizing, both organic and anorganic modifications are able to modulate the effect of thyroid hormones. This mechanism is a very effective way to encode a high grade of information entropy in rather small molecules.


Gereben B, Zavacki AM, Ribich S, Kim BW, Huang SA, Simonides WS, Zeöld A, Bianco AC. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev. 2008 Dec;29(7):898-938. doi: 10.1210/er.2008-0019. PMID: 18815314

Engler D, Burger AG. The deiodination of the iodothyronines and of their derivatives in man. Endocr Rev. 1984 Spring;5(2):151-84. PMID 6376077.

Piehl S, Hoefig CS, Scanlan TS, Köhrle J. Thyronamines--past, present, and future. Endocr Rev. 2011 Feb;32(1):64-80. doi: 10.1210/er.2009-0040. PMID 20880963.

  • $\begingroup$ This answer is great. It's technically complete and well-sourced. It doesn't actually answer the question I asked, but that is its only fault. $\endgroup$
    – Resonating
    Oct 27 '15 at 19:47

Iodine in us

Iodine is found in two main hormones, T3 and T4. They affect every part of the body, and are important for cell-cell signaling. Wikipedia says:

The thyronines act on nearly every cell in the body. They act to increase the basal metabolic rate, affect protein synthesis, help regulate long bone growth (synergy with growth hormone) and neural maturation, and increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness. The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.

Why do we have iodine in these hormones?

This is really what your question is. I have found several articles about this and what I found is Iodine is an important catalyst, and Iodotryosines evolved to be important hormones

First, of all, the use of iodine in organisms was ancient. Many prokaryotes and protists used it as a way to deal with reactive oxygen species. Iodide peroxidases were present in primitive oxygenic and photosynthetic Cyanobacteria about 3 - billion years ago. This is because Iodine is one of the most ancient antioxidants.

The thyroxine-like hormones seems to have evolved some 4 Mya in unicellular algae. However, its original function was not for cell-cell signaling as is the case for T3 and T4. It was originally to catalyze other biochemical reactions and scavaging free radicals. This all came about when tyrosine was first created. Iodine reacts with the tyrosine, and forms iodotryosines that were important catalysts for many biochemical reactions.

The first use of Iodotryosines for regulation could have been for ATPase in the mitochondria for non-verterbrate organisms. Also, for vertebrates, the regulation of mtRNA was regulated by iodotryosines.

Iodotyrosines can diffuse between cells very easily, and the development of TH-receptors leaded to the development of thyroxine hormones. Such hormones were used first for embryological development, metamorphosis (if this is the correct term) of amphibians, and more. The rest is really evolution! These hormones are present in virtually all organisms (except prokaryotes).


In summary, the use of iodine in hormones started with iodine in the first cells as they provide protection against free radicals and reactive oxygen species, while catalyzing biochemical reactions. Iodotyrosines evolved to be important for regulation in cells and finally important in cell-cell signaling.

If you have any more questions, please ask in the comments or we can chat in the Biosphere.


These are my sources and there is much more information on these articles. Note that I am not chemically correct about the form of iodine used so these articles have the correct information



  • $\begingroup$ Iodine helps balance out ROS production of metabolism, so when iodine is present, grow. That helps explain pretty much everything, I think. Nice answer. $\endgroup$
    – Resonating
    Oct 30 '15 at 13:19

here is an interesting article:

The accumulation of radioactive iodine by Amphioxus

summarizing the abstract: it's about cephalocordates that are not vertebrate, so they are close relatives (most related to the ancestors of) the vertebrate. The specific cephalocordate in question is amphioxus.The article talks about a specific gland called the "endostyle" of Amphioxus and it explored the homology with the subpharyngeal gland of the larval form of lampreys (an agnathan, the most primitive of vertebrate) called ammocoete. The sub pharyngeal gland is sort of the same thing as the thyroid. In fact this sub pharyngeal gland or thyroid is a defining characteristic of vertebrate. The abstract describes an experiment where they took the endostyle from amphioxus and implanted it into a salamander (and amphibian) and it had effects similar to the thyroid gland. This means that this mucous producing gland in the cephalocordates produces compounds that have effects similar to the thyroid

Why does the endostyle produce mucous? Because it is essential for their filter feeding (feeding by straining suspended matter and food particles from water).

Why concentrate iodine in the mucous, I don't know.

The other answers explain the function of iodine. This answer was to explain the evolution of iodine concentrating glands at the very beginning of our vertebrate ancestors.

  • $\begingroup$ Have a look at the article, I found an open source (linked above). $\endgroup$
    – Chris
    Feb 11 '15 at 19:18
  • $\begingroup$ nice! full text definitely beats abstract... $\endgroup$ Feb 11 '15 at 19:28
  • $\begingroup$ I went back and reread this paper, and it looks like the thyroid started as a gland that secreted mucus into the gut, so any signaling molecules would have to be gut-resistant, ruling out proteins and so on. Still not sure why iodine exactly, but this has helped narrow it down for me substantially. Nice find. $\endgroup$
    – Resonating
    Jun 3 '15 at 14:35
  • $\begingroup$ yea, and just for a comparison I guess GI peptide horomones are secreted into the blood (or lymphatics?)... given high blood flow to the GI when eating the guts get some of the peptide horomone back... presumably endostyle secretions were secreted into the gut and not the blood... $\endgroup$ Jun 4 '15 at 15:25
  • $\begingroup$ you know I've never read anything about GI peptide horomones (CCK, secretin, gastrin, GLP, etc) in primitive cordates... $\endgroup$ Jun 5 '15 at 15:25

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