What is Triiodothyronine (T3)?

Triiodothyronine, commonly referred to as T3, is a thyroid hormone that plays a crucial role in regulating various physiological processes within the human body. As a highly active and potent hormone, T3 impacts essential functions such as growth and development, muscle control, metabolism, maintenance of bones, body temperature, and heart rate. High or low T3 levels may indicate an underactive or overactive thyroid.

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Production of T3

T3 and thyroxine (T4) are crucial hormones produced by the thyroid gland that play essential roles in regulating metabolism and growth throughout the body. Approximately 80% of T3 in circulation is generated through the deiodination process, where an iodine atom is removed from T4 in peripheral tissues such as the liver, kidneys, and skeletal muscles. This conversion is facilitated by deiodinase enzymes, particularly type 1 deiodinase. The remaining 20% of T3 is directly synthesized and released by the thyroid gland itself.

Once in the bloodstream, the majority of T3 and T4 are bound to transport proteins, primarily thyroxine-binding globulin (TBG), along with smaller amounts bound to thyroid-binding prealbumin (TBPA) and albumin. These carrier proteins protect the hormones from degradation and facilitate their transport to target tissues. However, it's important to note that only the unbound or free fraction of T3 (about 0.3% of the total T3) is biologically active and able to interact with receptors in cells to exert its effects.

The production of thyroid hormones, T4 and T3, is regulated by a feedback loop. When T4 and T3 levels rise, they inhibit the release of thyrotropin-releasing hormone (TRH) from the hypothalamus and thyroid-stimulating hormone (TSH) from the pituitary gland. This feedback mechanism helps maintain a stable and consistent level of thyroid hormones in the body.

Figure 1. Production and action of thyroid hormone.
(Source: De Sibio, M. T. et al., 2014)

Mechanisms of Action

T3 exerts its effects on target tissues by binding to nuclear thyroid hormone receptors (TRs) present in the cell nucleus. This hormone-receptor complex interacts with specific DNA sequences known as thyroid hormone response elements (TREs), leading to the activation or repression of target genes. Through this genomic mechanism, T3 regulates the expression of genes involved in metabolism, growth, and development.

In addition to its genomic actions, T3 also exerts rapid, non-genomic effects on various cellular processes. It can modulate ion channels, enzyme activities, and signal transduction pathways, influencing cell function within seconds to minutes.