Thanks to a recent post by Rod we have a look at some of the current exploration of T2. PR
" Conclusion: Our findings from a healthy euthyroid population may point toward a physiological link between circulating 3,5-T2 and glucose metabolism."
"Moreover, enlarged heart weights indicate potential cardiac side effects of 3,5-T2 beyond hepatic thyromimetic actions. Altogether the observed thyromimetic effects of 3,5-T2 in several mouse TH target tissues raise concern about indiscriminate administration of 3,5-T2 as powerful natural hormone for the treatment of hyperlipidemia and pandemic obesity."
Not sure my brain can wrap around what you have written. But my endo told me there is no such thing as T1 or T2 only T3 and T4. Thought it must be time to look for a new endo!
That T1/T2 exist is not the question, only what they accomplish lacks any great understanding. Unfortunately it is not surprising an endo would be ignorant of the facts. PR
Well, these Pomeranians apparently have a means by which to assay T2 in the blood in euthyroid patients.
'3,5-T2 concentrations were measured by a recently developed immunoassay in sera of 761 euthyroid participants of the population-based Study of Health in Pomerania.'
Major LOL! In the UK the labs balk at testing fT3. Imagine the hoopla if a doctor wanted to know fT2!
Yes, I know there's a test but it is hyper expensive - even worse than T3. And, if it turned out you weren't converting your T3 to T2 - and therefore no T2 to T1 - what the hell would they do about it??? They can't even treat a simple T4 deficiency correctly.
Goosey, either you stayed up half the night or you wake up at cock's crow....
We had a nice big snow storm over here. I left for home early, struggled with the ice and snow to get home. Promptly had a couple of shots of vodka, a big bowl of soup and fell asleep by 5:30 p.m. My default in snow conditions is hibernation. I woke up at 11:30 p.m. to find the snow had stopped.
What to do when outside is a disaster and going to store to pick up milk is a fool's adventure? Sleep. I was disgusted with myself that I just did not have the 'balls' to get stuck in a snow drift while purchasing milk on my way home. There were people I met who were stuck for 3.5 hours getting to work. Good god........I thought, how are they going to go home? This is symptom of the sprawl of the human population. People live increasingly long distances from their jobs. Terrible at the best of times. Horrific when weather comes to town to play.
You have found information on the cost of a T2 test?
I guess people who take NDT are getting it all. The rest of us can cross our fingers and hope.
lol Both, actually! I have a new rescue dog - he arrived at lunchtime on Wednesday and has hardly slept since - very nervous and very hungry! I've spent most of the time since trying to reassure him and feeding him. He just stands and stares at me mournfully and hardly ever even lies down. I'm hoping he'll settle down some time soon so that I can get to bed!
I got stuck in a snow storm once. I lived in the heart of the country, miles from civilisation, and worked in a town 40 kms away. They told us to go home at lunchtime because a huge snow storm was on the way. It hit during the drive home. It was ok until I had to leave the main road and join a convoy of cars crossing the open country. It was slow but we were ok as long as we kept going.
However, we came to a hill, and a little 2CV about five cars ahead of me, chickened out and stopped. In a few seconds, it was completely snowed in. And so were all the cars behind him! Oh well, I had my packed lunch - which I hadn't had time to eat at work - a bottle of water, a book and a blanket, so I settled down until the tractors came to dig us out. lol I was driving a huge Renault 21 at the time, so I wasn't as vulnerable as the 2CV. So once they'd dug him out, I had no problem driving into the next village, and from thence home!
It was ages ago that I read about the test for T2 - two crashed computers ago - so I don't have any links to it.
Whether or not people taking NDT really do get all the thyroid hormones is debatable. But that doesn't help you if - like me - you can't tolerate any form of T4!
My mother-in-law used to look after rescue dogs and some of them were really insecure so she got a cage (with an open door) and they were happy to sleep in there.
Yes, I have considered a cage but they take up an awful lot of room. So, I compromised by getting a cardboard box, about his size and lying it on its side with his bedding Inside. He totally ignores it! He started by lying on the cold tiled kitchen floor - which is more like what he was used to in the shelter, and he has been in the shelter for 9 years! - then the tiled bedroom floor, then progressed to the bedroom carpet. But this afternoon, he is quite happy on a blanket on the wooden floor of my office. So, if that's what he wants... lol Early days yet, he will probably go through a lot of other spots before he finally settles.
T2 comes from deiodination of both T3 and rT3. So the amount appearing should be at least as much (in number of molecules) as T3 and possible quite a bit more.
The article mentions circulating T2. It seems to me that at least some T2 might never make it out of the cells in which it first appears.
I believe that though desiccated thyroid will contain some T2, the amount will be at the very tiniest level, far below that of T3. Indeed, I suspect the content might be so low as to be insignificant. A lot said about desiccated thyroid seems to be in an attempt to provide a justification for its use rather than the simple "because it works (better)". It would be good to know why so many find that, but until we do, let us not mis-claim.
I suspect the answer is that no-one knows. But it seems feasible that intra-cellular conversion to T2 would be unaffected by failure of DIO1 in liver and kidneys.
"If they cannot convert T4 to T3, would they be able to convert T3 to T2?"
The short answer is yes.
Grey, my understanding is that D1 and D2 up regulate and D3 down regulates or clears. D2 is supposedly several hundred times stronger than D1. Conversion of T4 to T3 is also affected by other factors. So if you had a problem with conversion (T4 to T3 by D1 + D2)) the down regulation or clearance by D3 would not be affected except possibly by less T3 to clear. Maybe Diogenes will set us all straight. PR
OK! Phew! That's a lot. That might have to wait until after Christmas because things are getting more and more hectic in this house! But I promise I will get down to it all in the New Year!
Thank you very much, PR. I'll let you know how I get on.
Thank you PR4NOW for posting those informative links. I found the second lecture particularly pertinent.
Slowing down the clearance of T3, converting T2 to T3 upregulation, chemical chaperones and Endoplasmic reticulation stress are at least being considered.
Food for thought: since T2 comes from rT3, how do you know that rT3 isn't the secret ingredient in NDT?
The D2 enzyme performs conversion of T4 to T3, but also rT3 to T2, INSIDE the cell. Therefore, rT3 could enter the cell and be converted to T2, which is apparently beneficial.
Re-reading what I wrote, it is part factual statement and partly conjecture. Let me restate the facts: the D2 enzyme is located within the cell. Also, D2 is know to convert T4 to T3. D2 is also known to convert rT3 to T2. jci.org/articles/view/29812...
The second part of my statement is conjecture: could rT3 enter the cell and be converted to T2? Or where does this rT3 conversion occur, if not inside the cell?
Interesting article thyroid.bwh.harvard.edu/rce... (p 781 on ubiquitination, second to last paragraph) "In fact, the decisive D2 property that characterizes its homeostatic behavior is a short half-life (approximately 40 minutes) (44) that can be further reduced by exposure to physiologic concentrations of its substrate, T4, and in experimental situations, reverse T3 or even high concentrations of T3 (44–50). This constitutes a rapid, potent generalized regulatory feedback loop that efficiently controls T3 production and intracellular T3 concentration based on how much T4 is available."
We seem to have two conversion circumstances (in the most general sense) - the one where the product is used within the cell, and the other where the product can be sent out from the cell to be circulated and used elsewhere. It is well-known that the liver cells convert T4 to T3 and make that T3 (or quite a lot of it) available to the bloodstream to be transported around. Cells like the hair follicle also convert T4 to T3 but I doubt any ever makes its way out of the follicle cells (as T3) - it is produced and used in situ.
At least, that is how it looks to me today. Maybe tomorrow I'll have changed my mind again...
Thanks, it is going to take me a few days to review the material, I just don't absorb things as fast as I used to. By the way you can get a lot of Dr. Bianco's articles at his website which I posted elsewhere here. Also you would enjoy his video if you haven't already watched it, also posted elsewhere here. PR
If you have any links I would love to see what you are reading, especially regarding T1 and brain function. The amounts of T2/T1 in NDT are unknown as far as I know. I have not seen an analysis from the last 10-15 years with current technology that gives us an accurate idea. At this point the vast majority would be produced extrathyroidally. T2 does seem to have an effect although there is still a limited understanding of exactly what it does. Still a lot of exploring going on. PR
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