3,5-Diiodothyronine Explained

3,5-Diiodothyronine (3,5-T₂) is an active thyroid hormone within the class of iodothyronines. It has two iodine atoms at positions 3 and 5 of its inner ring.

Biological effects

3,5-T₂ is an active thyroid hormone. It stimulates the TR-beta receptor for thyroid hormones and thus increases energy expenditure.^{[1] [2]} It has agonistic (thyromimetic) effects at myocardial tissue and pituitary, which results in 3,5-T₂ suppressing TSH release.^{[3] [4]} 3,5-T₂ is an allosteric regulator of the cytochrome c oxidase, the complex IV of the electron transport chain. It increases its activity by preventing the interaction of adenosine triphosphate (ATP) as an allosteric inhibitor.^[5]

Clinical significance

In nonthyroidal illness syndrome 3,5-T₂ concentrations are increased.^{[6] [7] [8] [9]} This could explain why patients with low T3 syndrome don't benefit from substitution therapy with thyroid hormones.^[7]

Notes and References

1. Goglia F . The effects of 3,5-diiodothyronine on energy balance . Frontiers in Physiology . 5 . 528 . 25628573 . 10.3389/fphys.2014.00528 . 2014 . 4292545. free .
2. Lombardi A, Senese R, De Matteis R, Busiello RA, Cioffi F, Goglia F, Lanni A . 3,5-Diiodo-L-thyronine activates brown adipose tissue thermogenesis in hypothyroid rats . PLOS ONE . 10 . 2 . e0116498 . 25658324 . 10.1371/journal.pone.0116498 . 2015 . 4319745. 2015PLoSO..1016498L . free .
3. Padron AS, Neto RA, Pantaleão TU, de Souza dos Santos MC, Araujo RL, de Andrade BM, da Silva Leandro M, de Castro JP, Ferreira AC, de Carvalho DP . Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues . The Journal of Endocrinology . 221 . 3 . 415–27 . Jun 2014 . 24692290 . 10.1530/JOE-13-0502 . 4045230.
4. Jonas W, Lietzow J, Wohlgemuth F, Hoefig CS, Wiedmer P, Schweizer U, Köhrle J, Schürmann A . 3,5-Diiodo-L-thyronine (3,5-t2) exerts thyromimetic effects on hypothalamus-pituitary-thyroid axis, body composition, and energy metabolism in male diet-induced obese mice . Endocrinology . 156 . 1 . 389–99 . Jan 2015 . 25322465 . 10.1210/en.2014-1604 . 4272399.
5. Arnold S. . Goglia F. . Kadenbach B.. 3,5-Diiodothyronine binds to subunit Va of cytochrome-c oxidase and abolishes the allosteric inhibition of respiration by ATP.. Eur. J. Biochem. . 252 . 325–330 . 1998 . 2 . 9523704 . 10.1046/j.1432-1327.1998.2520325.x. free .
6. Pinna G, Meinhold H, Hiedra L, Thoma R, Hoell T, Gräf KJ, Stoltenburg-Didinger G, Eravci M, Prengel H, Brödel O, Finke R, Baumgartner A . Elevated 3,5-diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors . The Journal of Clinical Endocrinology and Metabolism . 82 . 5 . 1535–42 . May 1997 . 9141546 . 10.1210/jcem.82.5.3939. free .
7. Dietrich JW, Müller P, Schiedat F, Schlömicher M, Strauch J, Chatzitomaris A, Klein HH, Mügge A, Köhrle J, Rijntjes E, Lehmphul I . Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling . European Thyroid Journal . 4 . 2 . 129–37 . Jun 2015 . 26279999 . 10.1159/000381543 . 4521060.
8. Langouche. L. Lehmphul. I. Perre. SV. Köhrle. J. Van den Berghe. G. Circulating 3-T1AM and 3,5-T2 in Critically Ill Patients: A Cross-Sectional Observational Study.. Thyroid. December 2016. 26. 12. 1674–1680. 27676423. 10.1089/thy.2016.0214.
9. Chatzitomaris. Apostolos. Hoermann. Rudolf. Midgley. John E.. Hering. Steffen. Urban. Aline. Dietrich. Barbara. Abood. Assjana. Klein. Harald H.. Dietrich. Johannes W.. Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming. Frontiers in Endocrinology. 20 July 2017. 8. 163. 28775711. 5517413. 10.3389/fendo.2017.00163. free.