An Overview Of Deiodinases And Thyroid Function

The Thyroid gland sits in the neck, in front of the windpipe, and has a shape that most people see as similar to a butterfly1.

Often overlooked, this gland plays a crucial part in the endocrine system, delivering hormones to the blood circulatory system that contributes to some of the most important functions in the body.

Metabolism is one of the primary areas that depend on the hormones produced by the Thyroid gland, but there are other bodily functions that also heavily relies on optimal levels of hormones secreted by the Thyroid.

There are only two primary hormones of the Thyroid gland2.

Thyroid tissue is responsible for the production of thyroxine, an inactive type of hormone that is converted into another Thyroid hormone, known as triiodothyronine. Triiodothyronine is the active hormone of the Thyroid gland and contributes to a great number of functions that are essential not only to the wellbeing of the human body, but also to life.

Thyroid hormones are produced when the pituitary gland sends Thyroid Stimulating Hormone to the Thyroid – the serum concentration of Thyroid Stimulating Hormone tells the Thyroid gland how much thyroxine to produce.

To understand Thyroid function and the importance that hormones produced by this gland plays in the body, as well as to obtain a better understanding of how different Thyroid disorders affect the body and why certain symptoms may develop in response to such disorders, we need to dig deeper into the biochemistry and other mechanics behind the Thyroid gland, as well as the different hormones that stimulates the gland, and those produced by the gland.

In this article, we want to turn our focus toward deiodinases, a group of enzymes that has a direct impact on Thyroid hormones present in the entire body – in particular, these enzymes serve a purpose of controlling the conversion of T4 Thyroid hormones, or thyroxine, into T3 Thyroid hormones, or triiodothyronine.

We will take a look at the different types of deiodinase enzymes, consider the possible implications currently presented in medical sciences associated with these enzymes, and also look at how different lifestyle factors, medications and health ailments can affect the function of deiodinase enzymes.

An Overview Of Thyroid Hormone Conversion And Deiodinases

Before we delve into the topic of how deiodinase enzymes are involved in Thyroid hormone function throughout the body, let’s first look at how the process of Thyroid hormone production works. The pituitary gland is situated at the back of the head and forms part of the brain.

This is one of the most crucial parts of the endocrine system, and releases a number of different hormones, acting as chemical messengers, to stimulate other glands; thus leading to the production of several different hormones.

Thyroid Stimulating Hormone is one of the main hormones produced in the pituitary gland.

The pituitary gland monitors levels of Thyroid hormone inside its tissue, and when the gland determines that levels of Thyroid hormones are running low, it produces Thyroid Stimulating Hormone.

The Thyroid Stimulating Hormone is secreted into the blood from the pituitary gland and then travels to the Thyroid gland. These hormones attach to the tissue within the Thyroid gland and deliver the “message” that more Thyroid hormones are needed by the body. In turn, the Thyroid gland starts to produce thyroxine, a primary Thyroid hormone.

Thyroxine is considered an inactive Thyroid hormone, due to the fact that it is not as potent as the other Thyroid hormone. This hormone does, however, still play a vital part in bodily functions as the body converts the thyroxine hormones into a more potent type of Thyroid hormone, known as triiodothyronine. This potent hormone then attaches to Thyroid hormone receptors found on every single cell contained in the human body.

It should be noted that the Thyroid gland is also able to produce triiodothyronine, but amongst the hormones produced by the gland, only approximately 20% consists of this hormone3.

This brings us to the subject of deiodinases. Deiodinases is a collective term used to describe a number of enzymes that are responsible for activating the conversion of thyroxine into triiodothyronine. Sometimes, deiodinase enzymes are also responsible for deactivating this conversion process.

The action performed by these enzymes depend on a variety of factors, with existing levels of Thyroid hormones present in the body being a particularly important factor that helps the enzymes determine when to activate and when to deactivate the conversion process.

The Three Types Of Deiodinase Enzymes

There are three main different types of deiodinase enzymes4 that can be found in the human body, each playing a particular role in the conversion of thyroxine into triiodothyronine. These three deiodinase enzymes include Deiodinase type 1, Deiodinase type 2 and Deiodinase type 3 – often referred to as D1, D2 and D3.

Let’s take a closer look at each of these enzymes to better understand their roles in Thyroid hormone regulation.

  • Deiodinase type 1 – The primary deiodinase enzyme that is responsible for converting thyroxine into triiodothyronine5. Deiodinase type 1 enzymes are found in tissue throughout the entire human body. The function of this enzyme is crucial to the purpose of the Thyroid gland and, of course, Thyroid hormones. It should be noted that deiodinase type 1 enzyme activity can be adversely affected by a number of different factors. Obesity, metabolic disorders and leptin resistance are known to cause impairments in the activity of these enzymes; thus leading to less thyroxine being converted to triiodothyronine. Additional factors that can impair deiodinase type 1 enzyme activity include depression, emotional stress, physiological stress, insulin resistance, diabetes, chronic fatigue syndrome, chronic pain, and also autoimmune diseases.

 

  • Deiodinase type 2 – Deiodinase type 2 plays the most crucial role in the pituitary gland, a part of the endocrine system that is responsible for determining how much activity should be exerted by the Thyroid gland to provide the body with adequate levels of Thyroid hormones. Deiodinase type 2 enzyme activity is the most potent between type 1 and type 2. These enzymes are also not as much affected by the use of certain medications as type 1 of this enzyme group is. It is also important to understand that, while deiodinase type 1 activity is impaired through obesity, diabetes, stress, depression and other factors, these particular issues rather causes an increase in Deiodinase type 2 enzyme activity.

 

  • Deiodinase type 3 – The last type of Deiodinase enzyme, known as Deiodinase type 3, is quite different from the first two types. While type 1 and type 2 of these enzymes promotes the conversion of thyroxine to triiodothyronine, Deiodinase type 3 rather has the opposite effect. This is a reverse enzyme that inhibits the conversion of thyroxine into the Thyroid hormone triiodothyronine. It is needed when levels of triiodothyronine become elevated in the human body, which can lead to hyperthyroidism symptoms – in such a case, deiodinase type 3 enzymes will impair the conversion process; thus reducing levels of triiodothyronine in the body. This type of Deiodinase enzyme is found in tissue throughout the whole human body except the pituitary gland.

Complications Faced In Medical Sciences Due To The Working Action Of Deiodinase Enzymes

When a patient exhibits symptoms associated with either Hyperthyroidism or Hypothyroidism, then a physician needs to perform a number of tests to provide an accurate diagnosis of the condition.

In addition to providing a diagnosis of either condition, a physician also needs to concern themselves with the fact that an underlying health problem, stress or other factor is contributing to the reduction or elevation of Thyroid hormones in the patient’s body.

When looking at the process of Thyroid hormone production, secretion and regulation, it is important not to overlook the importance of Deiodinase enzymes.

Unfortunately, this is also where some potential complications come into play. There are a few factors that both patients and physicians need to keep in mind when it comes to testing for Thyroid-related issues in a patient when they exhibit obvious symptoms that may signal the presence of an underactive Thyroid or an overactive Thyroid.

An example would be how the activity of D1 and D2 enzymes are affected through external factors. While obesity, stress, depression and similar factors are known to cause D1 activity to become reduced, leading to a lower conversion rate of thyroxine to triiodothyronine, the same factors cause an increase in D2 activity.

Since D1 is primarily active in all body tissue and plays an insignificant role in the pituitary gland, and D2 activity is primarily active within the pituitary gland, testing for TSH and specific Thyroid hormones may not always provide accurate data to be used in diagnosing a patient with a patient and identifying the most effective dose of medication for their condition.

Additionally, it is important to note that the presence of Deiodinase enzymes, as well as Thyroid hormones, in the body can greatly defer from one individual to another.

The physiology tends to defer between patients, which further complicates accurate diagnosis and, of course, appropriate dosage of pharmaceutical drugs and interventions to assist with treating Thyroid-related health ailments.

Providing More Accurate Screening For Thyroid Dysfunction

The data analyzed above provides a clear overview that physicians need to ensure they do not place all of their attention on considering an overview of Thyroid hormone levels in a traditional setting anymore. With more research becoming available on the topic of Thyroid dysfunction, new concerns are also risen.

It is no longer recommended to only perform a standardized set of blood tests to determine thyroxine levels and Thyroid Stimulating Hormone levels in the patient’s body, but additional tests are now recommended.

The level of triiodothyronine within the pituitary gland is almost always higher in concentration than in other bodily tissues.

Elevated levels of triiodothyronine in the pituitary gland can cause Thyroid Stimulating Hormone production to become reduced, yet hypothyroidism effects may be present in the rest of the body’s tissues.

Since stress, obesity and other risk factors exist that causes opposite effects in D1 and D2 enzymes, another concern comes up – when D1 enzyme activity is impaired, a reduction in triiodothyronine is observed in the overall body, but when these factors affect D2 enzyme activity, triiodothyronine levels in the pituitary gland becomes enhanced.

This causes a lower concentration of Thyroid Stimulating Hormone to be sent to the Thyroid – a chain reaction, where the Thyroid now no longer produces enough thyroxine or triiodothyronine.

Conclusion

Thyroid function is crucial for metabolism and overall cellular function, with each cell in the body containing a receptor specifically for Thyroid-related hormones.

Numerous conditions can affect Thyroid function, but when trying to understand these topics, simply looking at Thyroid hormones in general is not enough to provide a solid foundation to know how Thyroid dysfunctions work.

Further education about deiodinase enzymes will help individuals understand how the hormones of the Thyroid is affected and converted into appropriate hormones that are needed for cellular metabolism.

Knowledge about the actions of these enzymes will also provide a clearer understanding of Thyroid diseases, such as hyperthyroidism, hypothyroidism and autoimmune thyroiditis.

References

1 Bove, M., Stansbury, J. E., & Romm, A. (2010). Endocrine Disorders and Adrenal Support. Botanical Medicine for Womens Health, 186-210. doi:10.1016/b978-0-443-07277-2.00008-8

2 Mullur, R., Liu, Y.-Y., & Brent, G. A. (2014). Thyroid Hormone Regulation of Metabolism. Physiological Reviews, 94(2), 355–382. http://doi.org/10.1152/physrev.00030.20133 Thyroid gland. You And Your Hormones. http://www.yourhormones.info/glands/thyroid-gland/

4 Larsen, P. R., & Zavacki, A. M. (2013). Role of the Iodothyronine Deiodinases in the Physiology and Pathophysiology of Thyroid Hormone Action. European Thyroid Journal, 1(4), 232–242. http://doi.org/10.1159/000343922

5 DIO1 iodothyronine deiodinase 1 [Homo sapiens (human)]. U.S. National Library Of Medicine. 11 March 2018. https://www.ncbi.nlm.nih.gov/gene/1733

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