There is a strong general assumption in health forums that rT3 and T3 compete for the same binding receptor sites in cells. This article shows that this is not true: each molecule has its own specific receptor and there seems to be little crosstalk:
Specific Nuclear Binding Sites of Triiodothyronine and Reverse Triiodothyronine in Rat and Pork Liver: Similarities and Discrepancies*
WILMAR M. WIERSINGA INDER J. CHOPRA DAVID H. SOLOMON
The specific binding of [125I]T3 and [125I]rT3 to nuclear extracts of rat and pork liver was studied. The Ka values of the binding of T3 and rT3 to nuclear extracts were similar (0.65 ± 0.12 vs. 0.68± 0.10 x 109 M-1; P = NS), but the maximal binding capacity for T3 was smaller than that for rT3 (333 ± 36 vs. 1209 ± 338 fmolμmg DNA; P < 0.05). The amount of nonradioactive T4 required to cause a 50% displacement of [125I]T3 from the nuclear binding sites was, on a molar basis, 27 times greater than that of T3 in the case of pork liver and 110 times greater than that of T3 in the case of rat liver. Similarly, rT3- binding sites were highly specific. Relative to rT3,16- and a 100- fold greater molar excesses of T4 were required to cause a 50% displacement of [125I]rT3 from the n clear binding sites in pork and rat liver, respectively. Similarly, 700–2150 times more rT3 than T3 was required to obtain a 50% displacement of [125I]T3; in contrast, 50ndash;250 times more T3 than rT3 was needed to displace 50% specifically bound [I25I]rT3. Reduced glutathione and other sulfhydryl (SH)-reducing agents increased, whereas oxidized glutathione and SH-oxidizing or -binding agents decreased the binding of [125I]T3 and [125I]rT3 to nuclear extracts, with one exception. Dithiothreitol, a potent SH-reducing agent, reduced the binding of rT3, whereas it increased the binding of T3 to the nuclear binding sites. A 48-h fast was associated with a significant reduction in the maximal binding capacity of nuclear extracts for T3 (control vs. fasting rats, 589 ± 92 vs. 339 ± 50 fmol T3μg DNA; P < 0.05) and rT3 (1620 ± 162 vs. 693 ± 102 fmol rT3μg DNA; P < 0.005) without changes in affinity.
The data suggest that 1) there exist specific high affinity, low capacity nuclear rT3-binding sites in rat and pork liver which are distinct from the nuclear T3 receptors, and 2) rT3- and T3- binding sites are reduced in parallel during starvation.
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diogenes
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This is interesting. However this is only in the liver. As I understand it every cell in the body uses t3. Is it possible that this outcome could be different in different parts of the body? Ie the brain or gut.
I wouldn't think so as rT3 has a very short lifetime in the body compared with T3 and certainly with T4. I don't think Nature has altered since 1982. It's a sound piece of work.
Probably due to poor conversion of T4 to T3. Conversion is affected by thyroid loss so you get a double whammy of lack of hormone production by the gland and down regulation of body conversion. So excess rT3 can be produced at any level if conversion is poor enough and the body can't properly respond to offered T4..
Diogenes, would you comment on the links I submitted to Rod in this thread. It certainly sounds as if T3 and RT3 do compete in some way. healthunlocked.com/thyroidu...
Perhaps they do, but at the level of T3/rT3 effects on biochemical reactions in the cell, not the receptors per se. The evidence against receptor actions is quite clear. Also rT3 is cleared extremely quickly, far faster than either T3 or T4 so its action is likely to be fleeting.
We often see people saying that rT3 is the "brake" on T3 production. That is, instead of making more T3, the body decides to convert T4 into (relatively) inactive rT3.
I have difficulty with this idea because the obvious approach would simply be to not convert the excess T4 at all. Also, we make rT3 even when there is insufficient T4.
Do you have an explanation, a hypothesis, that can help to pull the many strands of opinion together?
Thank you, diogenes. So if someone has high reverse T3 due to high cortisol, etc., would you suggest they should stop taking T4 and perhaps any T3 as well until it's resolved?
First try to resolve the cortisol problem. This is probably causing the conversion problems. If cortisol sorted out, the rest should follow. Look at Henry Lindner's website. He talks about cortisol and thyroid a lot.
Perhaps you ought to know that with our encouragement Lindner sent in an article based on his beliefs and treatment regime. to stand alongside ours in Frontiers in Thyroid Endocrinology. It was rejected. It will take a long time to break down the doors of refusal to engage with the argument and then rely on the old dogmas. One has to tread carefully, which Anthony Toft in his latest opinion piece certainly did not.
The first thing to say is that if there is excess T4, it has to be got rid of somehow in a fashion that is safe for the cell. T3 is obviously not the way to go because that is the active hormone. Deactivation of T4 is done stepwise, 1 iodine atom lost at a time T4--T3 or rT3---T2 of at least three forms, only 1 active----T1-- then back to iodide and back to the thyroid to build up T4 and T3. Just removing T4 from a cell without deactivation wouldn't work - its a waste of iodine because the body would have to excrete it. I look at the process as running a bath with a leaky plug. T4 and T3 come out of the tap. T4 is converted to T3 and rT3 in the bath and the rT3 runs out through the leaky plug. Usually in health that's in balance. However, if the bath T4-rT3 conversion is too big, then rT3 will build up - the leakiness of the plug is not big enough to get rid of it all at once. Then I suppose some unknown biochemical competitions then occur in the bathwater which may in health feed back to the tap supply of T4 and T3. But that's in health. With T4 supplied as a tablet, there's no control as there is in health. More T4 given = more rT3 produced.
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