Thyroid UK

Rapid Responses to Reverse T3 Hormone in Immature Rat Sertoli Cells: Calcium Uptake and Exocytosis Mediated by Integrin

I just want to highlight a single phrase from this paper:

Until recently, rT3 was regarded as an inactive hormone, ...

I have long suspected that rT3 (reverse T3) might have some activity of importance. Although this paper concerns male rats - it does claim to identify an action.

PLoS One. 2013; 8(10): e77176.

Published online 2013 Oct 10. doi: 10.1371/journal.pone.0077176

PMCID: PMC3795021

Rapid Responses to Reverse T3 Hormone in Immature Rat Sertoli Cells: Calcium Uptake and Exocytosis Mediated by Integrin

Ana Paula Zanatta,1 Leila Zanatta,2 Renata Gonçalves,1 Ariane Zamoner,1 and Fátima Regina Mena Barreto Silva1,*

Toshi Shioda, Editor

1Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis-Santa Catarina, Brazil

2Universidade Comunitária da Região de Chapecó, Chapecó, Santa Catarina, Brazil

Massachusetts General Hospital, United States of America

* E-mail: rb.csfu@oterrab.anem

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: APZ LZ RG AZ FRMBS. Performed the experiments: APZ LZ RG. Analyzed the data: APZ LZ RG AZ FRMBS. Contributed reagents/materials/analysis tools: AZ FRMBS. Wrote the manuscript: APZ LZ FRMBS.


There is increasing experimental evidence of the nongenomic action of thyroid hormones mediated by receptors located in the plasma membrane or inside cells. The aim of this work was to characterize the reverse T3 (rT3) action on calcium uptake and its involvement in immature rat Sertoli cell secretion. The results presented herein show that very low concentrations of rT3 are able to increase calcium uptake after 1 min of exposure. The implication of T-type voltage-dependent calcium channels and chloride channels in the effect of rT3 was evidenced using flunarizine and 9-anthracene, respectively. Also, the rT3-induced calcium uptake was blocked in the presence of the RGD peptide (an inhibitor of integrin-ligand interactions). Therefore, our findings suggest that calcium uptake stimulated by rT3 may be mediated by integrin αvβ3. In addition, it was demonstrated that calcium uptake stimulated by rT3 is PKC and ERK-dependent. Furthermore, the outcomes indicate that rT3 also stimulates cellular secretion since the cells manifested a loss of fluorescence after 4 min incubation, indicating an exocytic quinacrine release that seems to be mediated by the integrin receptor. These findings indicate that rT3 modulates the calcium entry and cellular secretion, which might play a role in the regulation of a plethora of intracellular processes involved in male reproductive physiology.

Full paper freely available here:

9 Replies

Interesting and highlighting how much is still unknown about the actions and pathways of all the thyroid hormones.


Useful paper in that it points clearly not to T3 receptor binding competition but more specific effect on ion uptake in cells. If rT3 did anything, this is the sort of effect I suspected it might have - a parallel is T2 effect on mitochondrial activity. That is, purely biochemical and specifically aimed.


Does it then mean that we don't have to concern ourselfs about RT3 ? The way I always understood that high RT3 does not allow one to lose . RT3 has been complex subject to understand . So many different theories are written about it .


The work here indicates that rT3 has biochemical effects on cells. What we don't know is whether these effects are good or bad. I'm assuming that it is primarily a response to illnes., If you can do something about it in T4 or combo therapy to reduce rT3 then do so. For example, it's no use wasting excess T4 if all you do is make more rT3. In nonthyroidal illness of course rT3 is raised as a defense mechaism so there's nothing you can do about that except get better.



Thank you so much for clarifying a complex on going important discussion. Will we ever learn the role of RT3 ?

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This makes me furious...

Although this paper concerns male rats ...

The majority of people who suffer from thyroid problems are female. And yet these researchers are using only male subjects to experiment on.


Something I came across quite recently - an old link from 1986 :

Quote (emphasis is mine) :

For centuries experts have studied groups of males and applied the results to all of us. The trouble is, all of us aren`t male--more than half of us are female.

One of the most outrageous examples is going on right now at Rockefeller University in New York.

Researchers there are studying the effects of obesity on estrogen activity and the tendency for women to develop breast and uterine cancer. All the subjects being studied are male.

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In this particular instance, they didn't have much choice:

A Sertoli cell (a kind of sustentacular cell) is a "nurse" cell of the testicles that is part of a seminiferous tubule and helps in the process of spermatogenesis; that is, the production of sperm.

:-) :-)

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Oops - outed! I never read the paper! :D

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The last sentence does show it was not intended to generalise to women.

Although I see your point .


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