Found these newly published papers regarding the T3/T4 relationship, unfortunately I haven't the brain cells left to work it out! Perhaps some newly diagnosed hyper/hypothyroid people who don't have brain fog yet, might find it interesting!
All i can understand is that in rats (with thyroid glands removed) all the tissues that need T3 to work properly need a mix of both T4 and T3 from outside except the brain or pituitary which stops TSH production with only T4
so similarly in hypothyroid humans if given only T4, the TSH is suppressed plus the production of T3 is decreased but all other tissues are crying out for both T4 and T3
Im not sure if that is the conclusion from this study or not since I can only read the abstract and not the whole paper
sorry trying to read and understand the whole paper
These two papers are addressing different things. The first one shows that T4-T3 deiodinase enzymes are changed in their sensitivity to T4 for conversion to T3 in different tissues. This is done by the attachment of the modifying control protein ubiquitin to the enzyme. Eg in the hypothalamus this alters the behaviour of the enzyme to T4, compared with other tissues (these will have different reactions with ubiquitin and additionally there are 3 sorts of deiodinases in the body tissues specific to each area). This means that each area of the body has different mechanisms of conversion of T4 to T3 so that it is essential overall to assess FT4 and FT3 to determine if the body is working properly vis a vis thyroid functioning.
The second paper is concerned with genetic alteration of one of more of the deiodinases themselves in individuals which also affects the T4-T3 conversion efficiency where they occur. These are called polymorphisms - i.e. there are different forms in different individuals. To add to the complication, ubiquitination still occurs whatever the polymorphism, but of course the outcome depends on the exact form of the enzyme and how ubiquitin reacts with it. A hugely complicated situation with almost infinite solutions.
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