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Regulation of skeletal muscle mitochondrial activity by thyroid hormones

Just when you thought you'd got your head round T4 and T3...

Don't go asking your GP for T2. :-)

It is most excellent that someone is actually looking at the effects of other substances in the thyroid hormone family. The step-by-step conversions that occur in the body are obviously important, and the next-step products of conversion have so often been ignored.

Front Physiol. 2015; 6: 237.

Published online 2015 Aug 21. doi: 10.3389/fphys.2015.00237

PMCID: PMC4543916

Regulation of skeletal muscle mitochondrial activity by thyroid hormones: focus on the “old” triiodothyronine and the “emerging” 3,5-diiodothyronine

Assunta Lombardi,1,*† Maria Moreno,2,† Pieter de Lange,3 Susanna Iossa,1 Rosa A. Busiello,2 and Fernando Goglia2,*

Author information ► Article notes ► Copyright and License information ►

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3,5,3′-Triiodo-L-thyronine (T3) plays a crucial role in regulating metabolic rate and fuel oxidation; however, the mechanisms by which it affects whole-body energy metabolism are still not completely understood. Skeletal muscle (SKM) plays a relevant role in energy metabolism and responds to thyroid state by remodeling the metabolic characteristics and cytoarchitecture of myocytes. These processes are coordinated with changes in mitochondrial content, bioenergetics, substrate oxidation rate, and oxidative phosphorylation efficiency. Recent data indicate that “emerging” iodothyronines have biological activity. Among these, 3,5-diiodo-L-thyronine (T2) affects energy metabolism, SKM substrate utilization, and mitochondrial functionality. The effects it exerts on SKM mitochondria involve more aspects of mitochondrial bioenergetics; among these, respiratory chain activity, mitochondrial thermogenesis, and lipid-handling are stimulated rapidly. This mini review focuses on signaling and biochemical pathways activated by T3 and T2 in SKM that influence the above processes. These novel aspects of thyroid physiology could reveal new perspectives for understanding the involvement of SKM mitochondria in hypo- and hyper-thyroidism.

Keywords: mitochondria, lipid metabolism, uncoupling, thyroid hormones, diiodothyronines

Full paper available here:

20 Replies

Thanks, once again, for another excellent paper.


Yes... in fact there are studies showing that T2 may suppress TSH by itself:

Yeah, TSH, that thing that never fails and it's always a perfect marker of the thyroid hormone availability for each and every tissue in the body. If T2 suppresses TSH, there are two options: or TSH is not so perfect (well, we already knew that, didn't we?) or T2 does much more things that we thought.

In any case, this is pretty disturbing, as there are supplements easily available through completely legal ways (even Amazon) that include T2.

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Helvella..It was bad enough asking about T3!!!! I wouldn't dare mention T2 and T1 !!

( Armour thyroid contains small amounts of both!!) Thankfully my Endo knows all about such things.

However I must say that whatever it does has certainly kept me calm recently.

a) I had to negotiate getting out of Sainsbury's car park and 3 miles home in traffic in 1st gear as my gear lever had become all wobbly and apparently has a detached pin so is in for repair next week. ( I think someone was watching over me as it was green lights all the way!).....I'm enjoying the praise for how I managed the journey!

b) my cooker regulo has packed up so my lemon drizzle cake was a puddle in a tin and would you believe they don't make cookers that width now so I'm literally having to redesign my worktops to accommodate something that will fit ....a new cooker and worktops and maybe new tiles kitchen is seemingly going to get a welcome face lift.....and it's not feeling like a hassle ...I'm enjoying it.

So,whatever is in this's doing a great job!! x


But does Armour contain any T2 or T1? I have yet to see any evidence that the tablets contain any T2 or T1. Even if the original "wet" thyroids contained small amounts of T2 and T1 (and I believe they might contain very small amounts), it is not certain that it can survive the journey through the factory, being formed into tablets, distributed, and swallowed.

(I suspect that some of the chatter about thyroids containing T2 and T1 actually confuses DIT with T2, and MIT with T1. Wiki explains these reasonably well: )

Bets of luck with the car and the oven... :-(


Thanks Helvella.......lunch today curtesy of worktop slow cooker!!

I need to apologise about Armour and T2/T1 as I have surprisingly not found it on the patient leaflet or bottle which I was expecting to.

However I knew that I had read it and not dreamt it and so far have found reference to small amounts of T2, T1 and calcitonin being in all dessicated thyroid but is not measured and not taken out.

There is reference Page 41 "Stop the Thyroid Madness"..........

" Rumour occasionally goes through the mill that Dessicated thyroid is nothing more than T4 and T3 especially since nothing more than both are mentioned in the product paper insert.But Pharmaceuticals will assure you that T2,T1 and calcitonin are simply not measured and are not removed."

I am sure this is not my original source so am expecting there to be others as I have read quite a few books,but not planning to plough through them.However,we know that they are in minute amounts what ever part they play.

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Trouble is, if we have no idea how much, we can have little to no idea whether they are having any effect whatsoever. Understanding why so many people appear to do better on desiccated thyroid could be a huge breakthrough - but it might not be the obvious thyroid hormones at all.


Proteins? helvella, as they stick to whatever it is connected with Autoimmunity, that's if I remember correctly!


I feel for you with the gear lever thing. Many years ago I snapped off the van's gear lever while changing down into second and had to drive home with a pair of pliers clasped onto 2 inches of gear stick ... not fun.

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Wow .....I can't imagine how you coped with that one!!

I couldn't believe what had happened.I got blocked by a large 4x4 driver wanting my parking space and I couldn't see through it,round it or over it ( they crowd you out far too close ...scared someone else is going to grab the space) so was forced to reverse out and exit with a full lock on away from it to avoid every other car and kept stalling ....suddenly realising my gear lever had gone floppy....I can laugh now but how I got home through the town centre I can't remember......I do remember thinking to keep space between me and everyone else.

The biggest laugh is that the replacement pin costs approx £1 and the labour involved to get to it approx£100 +,however I'm not complaining if it keeps my car on the road's a part of me.

Happy Driving !


Oh I wish my Endo here did, I w been told by her to go and find a holistic cure for knowledge about all my health - she only concentrates on the

Liver ha ha and the Thyroid specialist was even less interested.

Who ever said France has the best health care system in the world? Certainly not me from my experiences so far.

My searches and answers are all thanks to having found Thyroid UK just over a year ago. The best places to research independently, after TUK, also are the American Hon Code and Trusted websites - well I think so, thus far,


I used to see Dr skinner and he said that Armour definitely contained calcitonin as he had specifically sent it for testing so guess one could assume it might contain other thyroid hormones too not only T3 and T4?


That is interesting. Thank you.

Howver, when it comes to calcitonin, that can be destroyed by enzymes in the gut. Which is why some calcitonin medicines were produced as nasal spray - to avoid the gut! Which makes me wonder how much can actually get into our bloodstreams?


I have just been looking at " Your Thyroid and how to keep it Healthy" by Dr.Barry - Durrant Peatfield which says it has been shown that T2 alone is effective in increasing liver metabolism. Whilst I fully realise that we are talking of T2 being a minor bit part I am reminded of the fact that since being on Armour Thyroid I am aware that the occasional niggles of my untreated gallstones has vastly decreased and I had forgotten about them.


There are several papers on T2:


That one is losing me!! I much prefer the way that BDP explains things......I can cope with that.


Is t4 converted into t2 as well as t3 by our bodies?


Not quite.

T4 is converted into T3 and reverse T3.

Then both T3 and rT3 are converted into T2.

The Wiki article isn't too bad:


Thanks, will read it.


thanks hellvella,so I guess it can be assumed as long as we have sufficient t3 then we're likely to make T2 ourselves?


Ooh Snap Helvella, I've also just posted today a link I found for metabolism. However I'm not as good as you at putting the right Acknowledgments and sources. I do my best though so I'm trying- yes I know, I'm very trying :-)

Also with your article, it just shows how much or many things is/are involved just with our metabolism and the Thyroid! It's quite scary really.


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