Liothyronine. By Boghog (Own work) [CC BY-SA 4.0 (http://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons

Liothyronine is a synthetic form of triidothyronine (or T3). T3 is a thyroid hormone with many physiological functions. It is present in the hypothalamus, adipose tissue and skeletal muscle tissue¹. T3 is associated with the regulation of glucose metabolism by modulating the response to insulin in the liver¹. It is also associated with the metabolism of cholesterol¹. It plays a role in the adaptation to cold in humans and animals, through the T3 receptors-alpha and -beta². T3 also regulates uncoupling protein-3, which is involved in the production of heat in brown adipose tissue and skeletal muscle³.

Thyroid hormones may also have important roles in the immune system. T3 levels in the immune cells of female (but not male) rats have been shown to decrease significantly in response to the administration of insulin⁴. Infusions of T3 have been shown to reverse the effects of thyroidectomy (i.e. reduced thyroxine turnover) in rats⁵. T3 is inhibited by type 3 iodothyronine deiodinase (D3), which inactivates this hormone by converting it to inactive T2⁶. A recent murine-cell in vitro study found that D3 is regulated by glucagon-like peptide-1 (GLP-1)⁶. Reduced free T3 levels are also associated with cardiac ischemia⁷. Supplemental T3 improved mitochrondrial function and cell viability in rat models of post-cardiac event ischemia⁸.

Deficiencies in the levels of thyroid hormones, including T3, are known as hypothyroidism. This condition may be associated with many adverse effects on health, including fatigue, weight gain and constipation. It may be associated with additional physiological effects such as mitochrondrial dysfunction or damage and hepatic cell death⁹. The administration of T3 reduced apoptosis in the liver cells, and oxidative damage in the mitochrondria, of rats with experimentally-induced hypothyroidism⁹. T3 may also promote the proliferation of liver cells¹⁰. Hepatocytes from rats fed T3 for two to seven days showed that this is mediated through beta-catenin phosphorylated by protein kinase A (PKA)¹⁰. Decreased thyroid hormone levels may also affect pain sensitivity and other CNS functions¹¹. Treatment with T3 (compared to a control treatment) significantly restored normal thermal (but not mechanical) pain thresholds in a mouse model of hypothyroidism¹¹. T3 also restored the normal levels of pain-regulating neurotransmitters in the anterior cingulate cortex of mice with hypothyroidism¹¹.

T3 is also associated with bone development¹². This is due to the fact that T3 receptors alpha and beta are present in bone cells¹². Some studies have demonstrated that younger animals with hypothyroidism exhibit bone malformations and dysfunctions¹². A study used a mutation to generate mice with inactive T3 alpha-receptors. This resulted in dysfunctional chrondrocyte proliferation and differentiation¹². However, mature chondrocytes were not affected by mutated T3 alpha-receptors¹². Thyroid hormones may also have cardioprotective functions, especially in response to adverse events¹³. Rats that underwent an experimental myocardial infarction treated with T3 and T4 for 26 days demonstrated a quicker return to normal cardiac function compared to similar untreated rats¹⁴. Treatment with T3 is also associated with the maturation of cardiac muscle cells derived from stem cells¹³.

References:

1. Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiological reviews. 2014;94(2):355-382.

2. Maslov LN, Vychuzhanova EA, Gorbunov AS, Tsybul'nikov S, Khaliulin IG, Chauski E. [Role of thyroid system in adaptation to cold]. Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova / Rossiiskaia akademiia nauk. 2014;100(6):670-683.

3. Branco M, Ribeiro M, Negrao N, Bianco AC. 3,5,3'-Triiodothyronine actively stimulates UCP in brown fat under minimal sympathetic activity. The American journal of physiology. 1999;276(1 Pt 1):E179-187.

4. Pallinger E, Csaba G. In vivo effect of insulin on the hormone production of immune cells in mice - gender differences. Acta microbiologica et immunologica Hungarica. 2014;61(4):417-423.

5. Nagao H, Sasaki M, Imazu T, Takahashi K, Aoki H, Minato K. Effects of triiodothyronine on turnover rate and metabolizing enzymes for thyroxine in thyroidectomized rats. Life sciences. 2014;116(2):74-82.

6. Akiyama S, Ogiwara T, Aoki T, Tsunekawa K, Araki O, Murakami M. Glucagon-like peptide-1 stimulates type 3 iodothyronine deiodinase expression in a mouse insulinoma cell line. Life sciences. 2014;115(1-2):22-28.

7. Novitzky D, Cooper DK. Thyroid hormone and the stunned myocardium. The Journal of endocrinology. 2014;223(1):R1-8.

8. Forini F, Kusmic C, Nicolini G, et al. Triiodothyronine prevents cardiac ischemia/reperfusion mitochondrial impairment and cell loss by regulating miR30a/p53 axis. Endocrinology. 2014;155(11):4581-4590.

9. Mukherjee S, Samanta L, Roy A, Bhanja S, Chainy GB. Supplementation of T3 recovers hypothyroid rat liver cells from oxidatively damaged inner mitochondrial membrane leading to apoptosis. BioMed research international. 2014;2014:590897.

10. Fanti M, Singh S, Ledda-Columbano GM, Columbano A, Monga SP. Tri-iodothyronine induces hepatocyte proliferation by protein kinase A-dependent beta-catenin activation in rodents. Hepatology (Baltimore, Md.). 2014;59(6):2309-2320.

11. Yi J, Zheng JY, Zhang W, Wang S, Yang ZF, Dou KF. Decreased pain threshold and enhanced synaptic transmission in the anterior cingulate cortex of experimental hypothyroidism mice. Molecular pain. 2014;10:38.

12. Desjardin C, Charles C, Benoist-Lasselin C, et al. Chondrocytes play a major role in the stimulation of bone growth by thyroid hormone. Endocrinology. 2014;155(8):3123-3135.

13. Yang X, Rodriguez M, Pabon L, et al. Tri-iodo-l-thyronine promotes the maturation of human cardiomyocytes-derived from induced pluripotent stem cells. Journal of molecular and cellular cardiology. 2014;72:296-304.

14. de Castro AL, Tavares AV, Campos C, et al. Cardioprotective effects of thyroid hormones in a rat model of myocardial infarction are associated with oxidative stress reduction. Molecular and cellular endocrinology. 2014;391(1-2):22-29.