Reverse T3 interacts with αvβ3 integrin receptor and restores enzyme activities in the hippocampus of hypothyroid developing rats

[helvella]

Possibly time finally to stop regarding reverse T3 (rT3) as an inactive substance?

evidence that rT3 is an active TH metabolite

Of course, every paper is subject to review, criticism of methods and logic, and the results being replicated.

Mol Cell Endocrinol. 2018 Jul 15;470:281-294. doi: 10.1016/j.mce.2017.11.013. Epub 2017 Nov 16.

Reverse T3 interacts with αvβ3 integrin receptor and restores enzyme activities in the hippocampus of hypothyroid developing rats: Insight on signaling mechanisms.

Domingues JT1, Cattani D2, Cesconetto PA2, Nascimento de Almeida BA2, Pierozan P3, Dos Santos K2, Razzera G2, Mena Barreto Silva FR2, Pessoa-Pureur R3, Zamoner A4.

Author information

1 Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Programa de Pós-Graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.

2 Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.

3 Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

4 Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Programa de Pós-Graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: [e-mail].

Abstract

In the present study we provide evidence that 3,3',5'-triiodothyronine (reverse T3, rT3) restores neurochemical parameters induced by congenital hypothyroidism in rat hippocampus. Congenital hypothyroidism was induced by adding 0.05% propylthiouracil in the drinking water from gestation day 8 and continually up to lactation day 15. In the in vivo rT3 exposure, hypothyroid 12-day old pups were daily injected with rT3 (50 ng/kg body weight) or saline until day 14. In the ex vivo rT3 treatment, hippocampal slices from 15-day-old hypothyroid pups were incubated for 30 min with or without rT3 (1 nM). We found that ex vivo and/or in vivo exposure to rT3 failed in restoring the decreased 14C-glutamate uptake; however, restored the phosphorylation of glial fibrillary acidic protein (GFAP), 45Ca2+ influx, aspartate transaminase (AST), glutamine synthetase (GS) and gamma-glutamate transferase (GGT) activities, as well as glutathione (GSH) levels in hypothyroid hippocampus. In addition, rT3 improved 14C-2-deoxy-D-glucose uptake and lactate dehydrogenase (LDH) activity. Receptor agonists/antagonists (RGD peptide and AP-5), kinase inhibitors of p38MAPK, ERK1/2, CaMKII, PKA (SB239063, PD98059, KN93 and H89, respectively), L-type voltage-dependent calcium channel blocker (nifedipine) and intracellular calcium chelator (BAPTA-AM) were used to determine the mechanisms of the nongenomic rT3 action on GGT activity. 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.

Copyright © 2017 Elsevier B.V. All rights reserved.

KEYWORDS:

3,3′,5′-triiodothyronine (reverse T(3), rT(3)); Integrin; Modeling; Nongenomic effects; Thyroid hormone; glutamate

PMID: 29155306

DOI: 10.1016/j.mce.2017.11.013

ncbi.nlm.nih.gov/pubmed/291...

Full paper (behind paywall) includes one diagram that is accessible:

sciencedirect.com/science/a...

An introduction to integrins is available here:

ncbi.nlm.nih.gov/books/NBK2...

Another post about an rT3 paper here:

healthunlocked.com/thyroidu...

[greygoose]

Well, we live and learn.

[helvella Administrator Thyroid UK in reply to greygoose]

Not sure how much I learn.

Tend to go AAAARRRGGGH! It is unbelievably complicated... and run off screaming.

[greygoose in reply to helvella]

Yes, I know exactly what you mean. You just get one thing firmly fixed in your head, and the next article/research contradicts it. I think I need a holiday!

[TSH110 in reply to helvella]

I’m afraid I shut off even before ploughing through that abstract - it was very hard going 😳 - and just felt sorry for the all the rats sacrificed to recent rt3 studies.