Alle medisiner for lavt stoffskifte består enten av T4 alene eller T4 og T3 i kombinasjon. T2 er også et stoffskiftehormon, men det lages i kroppen og ikke i kjertelen. Selv NDT (Thyroid) har minimalt med T2 i seg. Thyroidea Norge mener: Det er svært lite forskning å finne om T2. Men det lille som finnes viser at T3 og T2 fungerer på forskjellige måter og har ulik biologisk funksjon. Det er derfor viktig å se på muligheten for at en del stoffskiftepasienter kan bli bedre dersom de ikke bare får tilskudd av T3 men også av T2. Dessverre finnes det ingen medisiner der man får kun T2. Det finnes bittelitt i NDT, men ettersom T2 i en frisk kropp nesten utelukkende dannes gjennom de-jodinase utenfor skjoldbrusskjertelen er det svært lite T2 å finne selv i NDT. Thyroidea Norge mener derfor at man bør se på muligheten for å utvikle enten syntetisk T2 alene eller i kombinasjon med f eks T4 og T3.

Denne artikkelen beskriver godt hvordan T2 sammen med T3, rT3 og T4 er en av de stoffskiftehormonene som faktisk har en biologisk effekt, der hver av dem har forskjellige jobber. Merk at artikkelen henviser til artikler av F Goglia som vi har ført opp under
A. J. Hulbert, University of Wollongong, Australia, Research Online (2000)
Thyroid hormones and their effects: a newperspective
Utdrag s 22: It is the opinion of this reviewer that there are four iodothyronines that have signficant but not identical biological activities and these are T4, T3, rT3 and 3,5-T2

F. GogliaDipartimento di Scienze Biologiche ed Ambientali-Universita degli Studi del Sannio-Via Portí, Arsa, 11 82100 Benevento, Italy Biological Biological effects T2 Goglia
Abstract: This article is principally intended to describe the facts concerning the actions of 3,5-diiodothyronine (T2). Until recent years, T2, because of its very low affinity for thyroid hormone receptors (THR), was considered an inactive metabolite of thyroid hormones (TH) (thyroxine (T4) and triiodo-L-thyronine (T3)). Several observations, however, led to a reconsideration of this idea. Early studies dealing with the biological activities of this iodothyronine revealed its ability to stimulate cellular/mitochondrial respiration by a nuclear-independent pathway. Mitochondria and bioenergetic mechanisms seem to be major targets of T2, although outside the mitochondria T2 also has effects on carriers, ion-exchangers, and enzymes. Recent studies suggest that T2 may also affect the transcription of some genes, but again the underlying mechanisms seem to be different from those actuated by T3. The accumulated evidence permits the conclusion that the actions of T2do not simply
mimic those of T3 but instead are specific actions exerted through mechanisms that are independent of those actuated by T3 and do not involve THR

Biosci Rep. 2002 Feb
Thyroid hormones and mitochondria.
Goglia F1, Silvestri E, Lanni A.
Abstract: Because of their central role in the regulation of energy-transduction, mitochondria, the major site of oxidative processes within the cell, are considered a likely subcellular target for the action that thyroid hormones exert on energy metabolism. However, the mechanism underlying the regulation of basal metabolic rate (BMR) by thyroid hormones still remains unclear. It has been suggested that these hormones might uncouple substrate oxidation from ATP synthesis, but there are no clear-cut data to support this idea. Two iodothyronines have been identified as effectors of the actions of thyroid hormones on energy metabolism: 3′,3,5-triiodo-L-thyronine (T3) and 3,5-diiodo-L-thyronine (T2). Both have significant effects on BMR, but their mechanisms of action are not identical. T3 acts on the nucleus to influence the expression of genes involved in the regulation of cellular metabolism and mitochondria function; 3,5-T2, on the other hand, acts by directly influencing the mitochondrial energy-transduction apparatus. A molecular determinant of the effects of T3 could be uncoupling protein-3 (UCP-3), while the cytochrome-c oxidase complex is a possible target for 3,5-T2. In conclusion, it is likely that iodothyronines regulate energy metabolism by both short-term and long-term mechanisms, and that they act in more than one way in affecting mitochondrial functions.

S G Ball, J Sokolov and W W Chin (1997) 3,5-Diiodo-l-thyronine (T2) has selective thyromimetice effects in vivo and in vitro
Viser at T2 er effektiv i å senke TSH og har en annen biologisk funksjon enn T3.
ABSTRACT: Recent data have suggested that the iodothyronine, 3,5-diiodo-l-thyronine (T2), has selective thyro-mimetic activity. In vivo,T2 has been shown to suppress TSH levels at doses that do not produce significant peripheral manifestations of thyroid hormone activity. Furthermore, T2 has been shown to produce smaller increments in peripheral indices of thyroid status than does T3, when doses resulting in equivalent suppression of circulating TSH are compared.

Antonelli A1, Fallahi P, Ferrari SM, Di Domenicantonio A, Moreno M, Lanni A, Goglia F. 2011 3,5-diiodo-L-thyronine increases resting metabolic rate and reduces body weight without undesirable side effects.
Abstract Recently, it was demonstrated that 3,5-diiodo-L-thyronine (T2) stimulates the resting metabolic rate (RMR), and reduces body-weight gain of rats receiving a high-fat diet. The aim of this study is to examine the effects of chronic T2 administration on basal metabolic rate and body weight in humans. Two euthyroid subjects volunteered to undergo T2 administration. Body weight, body mass index, blood pressure, heart rate, electrocardiogram, thyroid and liver ultrasonography, glycemia, total cholesterol, triglycerides, free T3 (FT3), free T4 (FT4), T2, thyroid stimulating hormone (TSH) and RMR were evaluated at baseline and at the end of treatment. RMR increased significantly in each subject. After continuing the T2 treatment for a further 3 weeks (at 300 mcg/day), body weight was reduced significantly (p<0.05) (about 4 percent), while the serum levels of FT3, FT4 and TSH, were unchanged. No side effects were observed at the cardiac level in either subject. No significant change was observed in the same subjects taking placebo

Mangiullo R1, Gnoni A, Damiano F, Siculella L, Zanotti F, Papa S, Gnoni GV. 2010 3,5-diiodo-L-thyronine upregulates rat-liver mitochondrial F(o)F(1)-ATP synthase by GA-binding protein/nuclear respiratory factor-2.
Abstract Besides triiodothyronine (T3), 3,5-diiodo-L-thyronine (T2) has been reported to affect mitochondrial bioenergetic parameters. T2 effects have been considered as independent of protein synthesis. Here, we investigated the effect of in vivo chronic T2 administration to hypothyroid rats on liver mitochondrial F(o)F(1)-ATP synthase activity and expression. T2 increased state 4 and state 3 oxygen consumption and raised ATP synthesis and hydrolysis, which were reduced in hypothyroid rats. Immunoblotting analysis showed that T2 up-regulated the expression of several subunits (alpha, beta, F(o)I-PVP and OSCP) of the ATP synthase. The observed increase of beta-subunit mRNA accumulation suggested a T2-mediated nuclear effect. Then, the molecular basis underlying T2 effects was investigated. Our results support the notion that the beta-subunit of ATP synthase is indirectly regulated by T2 through, at least in part, the activation of the transcription factor GA-binding protein/nuclear respiratory factor-2. These findings provide new insights into the T2 role on bioenergetic mechanisms.
2009 Elsevier B.V. All rights reserved.

Mollica MP1, Lionetti L, Moreno M, Lombardi A, De Lange P, Antonelli A, Lanni A, Cavaliere G, Barletta A, Goglia F. 2009
3,5-diiodo-l-thyronine, by modulating mitochondrial functions, reverses hepatic fat accumulation in rats fed a high-fat diet
Abstract
BACKGROUND/AIMS:
Mitochondrial dysfunction is central to the physiopathology of steatosis and/or non-alcoholic fatty liver disease. In this study on rats we investigated whether 3,5-diiodo-l-thyronine (T2), a biologically active iodothyronine, acting at mitochondrial level is able to reverse hepatic steatosis after its induction through a high-fat diet.
RESULTS:
Stained sections showed that T2 treatment reduced hepatic fatty accumulation induced by a high-fat diet. At the mitochondrial level, the fatty acid oxidation rate and carnitine palmitoyl transferase activity were enhanced by T2 treatment. Moreover, by stimulating mitochondrial uncoupling, T2 caused less efficient utilization of fatty acid substrates and ameliorated mitochondrial oxidative stress.
CONCLUSION:
These data demonstrate that T2, by activating mitochondrial processes, markedly reverses hepatic steatosis in vivo.

Journal of Physiology (1997),505.2,pp.529-538
How the thyroid controls metabolism in the rat: different roles for triiodothyronine and diiodothyronines
Maria Moreno, Antonia Lanni, Assunta Lombardi and Fernando Goglia
These results indicate that T2s and T3 exert different effects on resting metabolism. The effects of T2s are rapid and possibly mediated by their direct interaction with mitochondria. Those of T3 are slower and more prolonged, and at least partly attributable to a modulation of the cellularity of tissues that are metabolically very active

Elena Silvestri, Maria Coppola, Federica Cioffi, and Fernando Goglia
Proteomic approaches for the study of tissue specific effects of 3,5,3′-triiodo-L-thyronine and 3,5-diiodo-L-thyronine in conditions of altered energy metabolism
Conclusions and perspectives: The biochemical and cellular mechanisms that underlie tissue specific actions of T3 and T2 are only beginning to be elucidated. However, the proteomic studies so far conducted separately analyzed the effects of T3 and T2 in different states of altered energy balance: changed thyroid state and over-nutrition, respectively To further characterize and compare the molecular and biochemical pathways that underlie T3 and T2 metabolic actions, T3 and T2 themselves should be used in the same experimental design in comparative approaches so to highlight putative common effects or iodothyronine-specific one.

Fernando Goglia, 2015
The effects of 3,5-diiodothyronine on energy balance
Introduction: …..This article is particularly intended to describe the effects of the 3,5 diiodo-L-thyronine (T2) on energy balance
3,5-diiodo-L-thyronine (T2) T2, a naturally occurring diiodothyronine, is a product of a currently unknown enzymatic process most probably utilizing T3 as its precursor (Moreno et al., 2002). Some years ago surprising results were published showing that (among a lot of iodothyronines tested) T2, at a very low concentration (pM), induced a rapid stimulation of oxygen consumption in perfused livers isolated from hypothyroid rats. In the same study, it was shown that T3 showed a similar effect but this effect was largely abolished by the addition of an inhibitor of D1 deiodinase, while the effect of T2 was not. Moreover, T2 exerted its effect more rapidly than T3 …

Maria Coppola, Daniela Glinni, Maria Moreno, Federica Cioffi, Elena Silvestri, and Fernando Goglia, 2014
Thyroid hormone analogues and derivatives: Actions in fatty liver
Conclusion: (…) Notably, the hypolipidemic effect of T2 is associated with a potent ability in both preventing and reducing fatty liver. Increasing evidence supports TH derivatives and analogues as attractive active agents that could be taken into consideration for the establishment of new treatments in the counteraction of metabolic disorders, such as T2DM, obesity and NAFLD, thus clinical trials are desirable.

Lombardi, A.; Lanni, A.; Silvestri, E.; Lange, P. d.; Goglia, F.; Moreno, M.
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry – Immunology, Endocrine and Metabolic Agents) 2006

3, 5-Diiodothyronine: Biological Actions and Therapeutic Perspectives
Abstract: The purpose of this review is to summarize the current state of knowledge concerning the biological activities of 3, 5-diiodothyronine (T 2) and its potential use as a pharmacological agent. Until recent years, T2 was considered an inactive metabolite of thyroid hormones thyroxine (T4) and triiodo-L-thyronine (T3). Several observations, however, led to a reconsideration of this idea. Early studies dealing with the biological activities of this iodothyronine revealed its ability to stimulate cellular/mitochondrial respiration, essentially by a nuclear-independent pathway. Mitochondria and the energytransduction apparatus seem to be major targets of T2, although outside the mitochondria T2 also has effects on carriers, ion-exchangers and enzymes. Recent studies suggest that T 2 may also affect the transcription of some genes, but again the underlying mechanisms seem to differ from those actuated by T3. The accumulated evidence permits the conclusion that the actions of T2 do not simply mimic those of T3 but instead are specific actions exerted through mechanisms that are independent of those actuated by T3 and do not involve thyroid hormone receptors. In addition, very recent evidence leads us to suggest that T2 may be a potentially useful agent for the treatment of diet-dependent overweight (and the consequent hypertriglyceridemia and high cholesterol level) without inducing thyrotoxicosis.