reverse T3 (rT3)

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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reverse T3 (rT3)

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reverse T3
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Researchers from the USA pre-published a paper recently, proposing that organ-specific complications of COVID-19 infection and vasculopathy may be the action of rT3 on actin polymerization (Davis et al., 2021). rT3 is elevated - and used as a biomarker - in fluoride poisoning (Lin et al., 1991, 1992; Sashi and Singla, 2013a, b).


Fröhlich E, Wahl R - "Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients" Front Endocrinol (Lausanne). 12:587518 (2021)

Davis PJ, Lin HY, Hercbergs A, Keating KA, Mousa SA - "Possible Contributions of Nongenomic Actions of Thyroid Hormones to the Vasculopathic Complex of COVID-19 Infection" Endocr Res. 2021 Nov 14:1-6. doi: 10.1080/07435800.2021.1972307 77. ... 21.1972307


Lin Jin, Lin Fafu, Zhao Hongxin, Jiang Jiyong, Xu Xunfeng - "A study on the relationship between serum rT3 and environmental iodine or fluoride levels" Endemic Disease Bulletin (3):68-70 (1992) ... ?id=720441

Lin Fa-Fu, Aihaiti, Zhao Hong-Xin, Lin Jin, Jiang Ji-Yong, Maimaiti, Aiken - "High-fluoride and Low-iodine Environment and Subclinical Cretinism in Xinjiang" Endem Dis Bul 6(2):62-67 (1991)
English Translation in: ICCIDD Newsletter, Volume 7 Number 3 (August 1991) ... F-1991.pdf

Shashi A, Singla S - "Syndrome of Low Triiodothyroinine in Chronic Fluorosis" International Journal of Basic and Applied Medical Sciences 3(1):152-160 (2013)
FULL PAPER: ... 1594834242

Shashi A, Singla S - "Clinical and Biochemical Profile of Deiodinase Enzymes and Thyroid Function Hormones in Patients of Fluorosis" Australian Journal of Basic and Applied Sciences 7(4): 100-107 (2013)

Thyroid (extra info)

Domingues JT, Cattani D, Cesconetto PA, Nascimento de Almeida BA, Pierozan P, Dos Santos K, Razzera G, Mena Barreto Silva FR, Pessoa-Pureur R, Zamoner A - "Reverse T3 interacts with αvβ3 integrin receptor and restores enzyme activities in the hippocampus of hypothyroid developing rats: Insight on signaling mechanisms" Mol Cell Endocrinol 470:281-294 (2018)
"Using molecular docking analysis, we found rT3 interaction with αvβ3 integrin receptors, nongenomically activating signaling pathways (PKA, CaMKII, p38MAPK) that restored GGT activity. We provide evidence that rT3 is an active TH metabolite and our results represent an important contribution to elucidate the nonclassical mechanism of action of this metabolite in hypothyroidism."

Sabatino L, Lubrano V, Balzan S, Kusmic C, Del Turco S, Iervasi G - "Thyroid hormone deiodinases D1, D2, and D3 are expressed in human endothelial dermal microvascular line: effects of thyroid hormones" Mol Cell Biochem 399(1-2):87-94 (2015) doi: 10.1007/s11010-014-2235-8. Epub 2014 Oct 11. PMID: 25304215.
"rT3 significantly inhibited DIO1 at 1 nM concentration (p < 0.01) and stimulated DIO1 at 10 nM dosage (p < 0.001)...These findings might be of significant clinical relevance, given the important regulatory role of the endothelium as first barrier to the bloodstream."


The increase of rT3 is much more pronounced following the administration of TSH (Kühn et al., 1988).

Kühn ER, Decuypere E, Iqbal A, Luysterborgh D, Michielsen R - "Thyrotropic and peripheral activities of thyrotrophin and thyrotrophin-releasing hormone in the chick embryo and adult chicken" Horm Metab Res 20(3):158-62 (1988) doi: 10.1055/s-2007-1010782. PMID: 3133299


Gq/11 is activated by slightly elevated TSH concentrations.
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