How does thyroid hormone find its way into the brain?

How does thyroid hormone find its way into the brain?

We see lots and lots of thyroid hormone blood test results here. And understandably.

The brain is separated from our blood supply by the blood-brain barrier (BBB). This paper talks about an active process of transporters "pumping" thyroid hormones across the BBB - and what fails to work if that process does not happen.

We never see any measurement of thyroid hormone levels within the brain (understandably - not the sort of thing that can be done in two minutes in the phlebotomy unit). We end up relying on the subjective measure like how we feel. And, maybe, how the functioning of the brain affects other things like mood, balance, vision, hearing, muscle control, etc. It might be interesting to know what the brain thyroid hormone levels are - but we are not going to find out any time soon.

It is also interesting that the transporters also handle rT3. So does rT3 really have a function? Why else would it be actively transported into the brain?

The "aromatic amino acids" mentioned are:

Among 20 standard amino acids:

. phenylalanine

. tryptophan

. histidine

. tyrosine

Others:

. thyroxine

. 5-hydroxytryptophan

. L-DOPA

I warn you that some of the paper could be upsetting in its description of the effect on some people of transporter mutations.

How does thyroid hormone (TH) find its way into the brain? Although it has been known for a long time that TH is crucial for normal brain development, the exact molecular mechanisms involved in TH transport in the brain have remained elusive until recently. Early studies showed selective and saturable accumulation of TH in particular brain regions, suggesting that active transport processes are required for TH entry across the blood-brain barrier (BBB) and into brain cells (1). The discovery that TH transporter proteins located in the plasma membrane are required for cellular entry of the hormone has advanced our understanding of TH physiology. Thus, TH transporters mediate transport not only across the BBB but also into each individual cell of the brain.

Many transporters have been identified that accept a wide range of substrates, including TH (2). Monocarboxylate transporter 8 (MCT8) and its homolog, MCT10, are important exceptions, showing a high activity and specificity for TH (3, 4). MCT10 shows preference for T3 over T4, but also transports aromatic amino acids. MCT8 transports different iodothyronines (T4, T3, rT3, 3,3'-T2) with similar efficiencies but does not appear to transport aromatic amino acids.

jcem.endojournals.org/conte...

If you were interested in that, you might find this also of interest:

jcem.endojournals.org/conte...

... and the links from that page.

Rod

13 Replies

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  • ...very interesting Rod - could have so many implications. In my simplistic thoughts I am wondering if being on T3 only is depriving the brain of T4 - maybe that is not what nature intended....

  • On the other hand, if your brain is not converting T4 to T3 adequately, it might be essential for some people to at least take mostly T3?

    (It appears some cells in the brain can take T4 in and then release T3 to be used by other cells, much as the liver and some other non-brain tissues do.)

    But you are, I feel, right to ask the question. It has always been perplexing to me that T3-only is even possible!

    Note: This is a simple discussion and NOT saying anyone on T3-only should change.)

    Rod

  • Rod, lots of us survive on less than optimal amounts of various hormones, (I would be dead by now if that were not so, although at my worst, I did expect that, fairly SOON!) so it's no surprise to me that we can survive on T3 only. Yes maybe we would be a bit or a lot more optimal with all the right proportions of whatever substance it is, but bodies are clearly fairly adaptive.

  • ...I am on T3 only and have felt well/better. If you do come across further research stating the need for T4 then please do let us know ! Perhaps my thyroid is still producing T4 - as demonstrated in my last blood test - even after being T3 only for some time. It just wasn't converting...oh well the mysteries continue....and we continue to learn. Love thought provoking posts Rod - thank you......

  • Isn't this also part of the argument about using NDT instead of the synthetic variants?.. it has (a very little) T1 and T2 plus calcitonin which is more like what your own production would have (although admittedly not in perfect proportions.)

    I have had, and now again clearly do have high RT3, and have been down the "clearing" route myself before, I did get the clearing effect fairly dramatically as expected, and did feel pretty "sorted" after, even after weanaing off T3 altogether, but like plenty of others, it's keeping that under optimal levels that's the problem... fine if you have a darned good idea of the cause (Circadian rhythm, a specific medical condition or whatever), but if you can't get rid of that cause (mine is most probably my chronic pain & osteoarthritis) then, sure as eggs is eggs it's going to come back like mine did (I presume, I didn't bother spending the money again to find it out!), and I have taken the attitude of forgetting about it, and (in simplistic terms) ensuring I have enough supplementary T3 (from NDT) and the other thyroid hormones to overcome it's effect of shutting down metabolism (as it does in hibernating bears!) :-(

  • I wonder if any of the calcitonin gets through the gut?

    Also, whether porcine calcitonin works in humans the same as human calcitonin?

    From the earliest days of reading about thyroid hormone, it has been difficult to understand quite why the assumption T4 alone is sufficient took hold so strongly in the world of medicine. I'd be much more accepting if the attitude were "Well, a lot of people can get by on T4-only." - leaving it open that adding in some T3 as well is a perfectly reasonable option in those who don't "get by". Indeed, I'd say I am pretty much equally amazed by both T4-only and T3-only!

    Rod

  • Do we know the % of people treated with T4 only that do well versus those that do not?

    I suspect not. I'm on the early days of taking T4

    [12ug due to go to proper 25 dose soon- my own approach ]

    and find it makes me muzzy and sensitive tongue, but I'm trying to ignore this and press on.

    I do sense more strong heartbeats, from time to time, and slightly better energy so hope this means some conversion is occuring to T3. Still crashing PM though.

    My fallback is to get RT3 checked eventually - but it's pricey [>£200]

  • With the number of people who have been taking levothyroxine only for many, many years and suddenly pop up here, I'd certainly be interested. So many of them say they have never been 100%. Yet I have met people who seem to have no problems with it at all. Maybe me? I'll reserve final judgement... :-)

    Rod

  • How long use before taking T4 makes stopping it a problem?

    I know hormones can take months to self regulate after being added in- but presumably many users have stopped without problems, apart from trasnsient effects ie: much like going onto it. No mention from GP at the time, on this

    I know, from this site, that adding in T3 can assist in some cases of T$ not working ot being well tolerated- but also that T3 is far from easy to get onto- in the present thyroid climate in the NHS.

  • Definitely a question. There certainly are cases of people no longer needing any thyroid hormone supplementation. So far as I know, there has not been enough research to clearly say anything much - but would would love to be proved wrong by a good paper/link!

    Rod

  • I was fine for years on t4 only. It was when I was diagnosed with stress induced sarcoidosis and treated with Pred that I noticed a big difference. Apparently Pred messes up many things. But my adrenals are not working properly so I must continue with it. I am hoping that an addition of t3 might help.

  • So , if there is a mutation in mct8 , how you can transport t3 to the brain ?

  • Might still have MCT10. Or there are other ways in which it can be transported either not yet known, or now covered by the paper?

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