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Author Topic: Study: proof that reverse T3 inhibits T3/T4 cells (finally)?  (Read 2825 times)

Kierkegaard

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Study: proof that reverse T3 inhibits T3/T4 cells (finally)?
« on: October 06, 2018, 02:10:49 am »
Kent Holtorf cites this study in one of his presentations:

The uptake and efflux of reverse triiodothyronine (rT3) in JAr cells were investigated. Uptake of 125I-rT3 was time dependent and reversible with a saturable component of around 70 per cent of total uptake after 30 min of incubation. Efflux was not saturable. Kinetic analysis of the initial specific uptake rates revealed an uptake process with a Michaelis constant of 3.04+/-0.53 microM (mean+/-SEM, n=15) and a corresponding maximum velocity of 9.65+/-2.49 pmol/min/mg protein (n=15). Uptake of rT3 was stereospecific, but not specific for rT3, as unlabelled L stereoisomers of thyroid hormone analogues were more effective as inhibitors of 125I-rT3 uptake than rT3. Unlabelled T3 and thyroxine (T4) (10 microM) reduced cellular uptake of 125I-rT3 by around 82 and 74 per cent, respectively. The calculated inhibition constants Ki were 1.23+/-0.29 microM (n=4) and 0.66+/-0.19 microM (n=4) for T3 and T4, respectively. Similarly, rT3 reduced cellular uptake of 125I-T3 and 125I-T4 by 34 and 23 per cent, respectively. The calculated inhibition constants Ki were 1.75+/-0.55 microM (n=8) and 1.08+/-0.36 microM (n=8) for the inhibition of 125I-T3 and 125I-T4 uptake, respectively. Reverse T3 inhibited efflux of 125I-T3 from the cells by around 20 per cent, but did not inhibit efflux of 125I-T4. These results suggest that uptake of rT3 in JAr cells may occur via a single, saturable membrane carrier, which also interacts with T3 and T4, while efflux of rT3 may occur by passive diffusion.

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The reason I'm looking for something like this is to explain why some people have bad effects from T4-only medications, such as levothyroxin.  The only other alternatives are pretty obscure references, like Ray Peat, not exactly known for orthodox opinions, who cites a study (though the abstract doesn't reveal this particular statement) in saying that brain slices administered T4 showed a 6% reduction in cellular respiration, which he used as evidence that T4 without the proper ability to convert to T3 (i.e., poor liver function, ironically part of the hypothyroid picture for many patients) causes more harm than good.

As excellent a researcher as Peat is, nowhere does he say that rT3 inhibits cellular uptake of thyroid hormone, T3 or T4.

Thoughts?
"The same thing that makes you live can kill you in the end." -- Neil Young

March 2014: Dx low T (158ng/dl)
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2016: chronic fatigue, unspecified

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Osprey

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Re: Study: proof that reverse T3 inhibits T3/T4 cells (finally)?
« Reply #1 on: October 06, 2018, 02:37:14 am »

The title of the study is: Uptake of reverse T3 in the human choriocarcinoma cell line, JAr.

Wikipedia tells me that Choriocarcinoma is a malignant, trophoblastic cancer, usually of the placenta.

Seems like a stretch to apply this to in vitro normal cells of every other type.

The late Dr. Kenneth Blanchard told me that he was convinced that the reason that many patients did poorly on T4 only meds was the fillers and additives in the different manufacturer's formulations. He said that he saw dramatic differences in patient responses to different T4 only meds.  His favorite T4 med was Tisosint, but after the price of that went through the roof he preferred Levoxyl or Mylan.  Definitely steer clear of anything with povidone in it. After he told me this I actually went through the FDA database and created a spreadsheet with a list of all the inactive ingredients of every FDA approved thyroid medication whether it be T4 only or NDT.

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Re: Study: proof that reverse T3 inhibits T3/T4 cells (finally)?
« Reply #1 on: October 06, 2018, 02:37:14 am »


Kierkegaard

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Re: Study: proof that reverse T3 inhibits T3/T4 cells (finally)?
« Reply #2 on: October 06, 2018, 02:56:15 am »

The title of the study is: Uptake of reverse T3 in the human choriocarcinoma cell line, JAr.

Wikipedia tells me that Choriocarcinoma is a malignant, trophoblastic cancer, usually of the placenta.

Seems like a stretch to apply this to in vitro normal cells of every other type.

Yeah, I thought the same thing.  But it's better than nothing.  It'd probably be best to lean agnostic on this subject given the dearth of data.
 
Quote
The late Dr. Kenneth Blanchard told me that he was convinced that the reason that many patients did poorly on T4 only meds was the fillers and additives in the different manufacturer's formulations. He said that he saw dramatic differences in patient responses to different T4 only meds.  His favorite T4 med was Tisosint, but after the price of that went through the roof he preferred Levoxyl or Mylan.  Definitely steer clear of anything with povidone in it. After he told me this I actually went through the FDA database and created a spreadsheet with a list of all the inactive ingredients of every FDA approved thyroid medication whether it be T4 only or NDT.

I tried Tirosint, and had the same reaction increasing the dose as I did with Levoxyl and levothyroxine.  I suppose this could be the case with a good number of people, but in my case it seems to go further.  I'm particularly interested in the lowering of cellular respiration that Peat talked about.  Given that mitochondria (which are essential for respiration) and thyroid are mutually reinforcing, there's something to the string of research he's found on the fringes, IMO.
"The same thing that makes you live can kill you in the end." -- Neil Young

March 2014: Dx low T (158ng/dl)
September 2015: Dx hypothyroidism, other adrenal hypofunction
2016: chronic fatigue, unspecified

Depression and anxiety guide: http://www.peaktestosterone.com/Help_Anxiety_Depression

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Re: Study: proof that reverse T3 inhibits T3/T4 cells (finally)?
« Reply #2 on: October 06, 2018, 02:56:15 am »