Are rats and humans really comparable?

Just curious, because I have been reading so much about how levothyroxine fails to restore euthyroidism in all tissues. However, all studies I have come across have examined thyroidectomized rats. But, can rats really be compared to humans? As far as I know, rodents have a very fast metabolism (I used to have hamsters as a child), meaning their thyroid gland must produce a lot more T3 than human thyroid glands...? So, are rats really comparable to humans in this respect? I was particularly hoping that diogenes would chime in if still active on this forum (I have read and learned a lot from his previous posts and articles).

ncbi.nlm.nih.gov/pmc/articl...

[helvella Administrator Thyroid UK]

Thyroid is a fundamental part of all vertebrates - and some pre-vertebrates.

Many of the genes associated with thyroid are highly conserved over evolution and stretch back a long, long way.

Therefore, we should very much expect rats to have quite a bit in common with humans. I think we would be surprised if they didn't have thyroids. If they didn't produce T4 and T3. If T4 and T3 didn't have broadly similar effects.

But the differences might be every bit as important when we do research.

TSH is not identical.

Thyroid binding globulin which is so important in humans is significantly different in rats.

I did a very quick search and found the paper below. Not ideal - but it starts by pointing out differences between rats and humans.

Human relevance of follicular thyroid tumors in rodents caused by non-genotoxic substances

sciencedirect.com/science/a...

[jimh111]

The experiment on rats demonstrates that levothyroxine monotherapy does give euthyroidism in all tissues. However, rats have a higher T3 / T4 ratio than humans so we would expect effects to be lesser in humans. The rat experiments show the principal but the degreeay be different between rats and humans.

[helvella Administrator Thyroid UK in reply to jimh111]

One study that was widely reported when first published in 1995.

Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats.

europepmc.org/article/MED/8...

[radd]

TiredThyroid50,

Yes, I have often wondered this too but guess they have to perform research and hopefully the different effects and regulatory systems are taken into consideration.

As helvella has mentioned it is known the binding proteins and their role differs between species.

Some animals only have albumin to transport thyroid hormone from synthesis to the target cells, whereas we humans have albumin, transthyretin (TTR), and thyroxine-binding globulin (TBG), although there have been reports of humans lacking albumin or TBG and remaining asymptomatic in some sort of evolutionary side step.

Although not specifically about rats, this is an interesting paper regarding the evolution of transporter proteins 😁

ncbi.nlm.nih.gov/pmc/articl...